Michael Zuscik, PhD

Professional Titles

• Mack Clayton Professor
• Vice Chair, Research
• Director, Colorado Program for Musculoskeletal Research

Recognitions

• Laut Honors Scholar, Wheeling Jesuit University (1987)
• Physics Departmental Award, Wheeling Jesuit University (1987)
• Reverend Frank R. Haig, S.J. Science Award, Wheeling Jesuit University (1987)
• Alpha Sigma Nu, National Jesuit Honor Society (1987)
• Finalist, F. Merlin Bumpus Young Investigator Award, Cleveland Clinic Foundation (2000)
• Marvin Hoffman Faculty Mentoring Award, University of Rochester (2006)
• NIH Undergraduate Scholarship Program Mentoring Award, NIH (2007)
• Distinguished Alumni Award, Wheeling Jesuit University (2016)

Research Interests

The central focus of our research can be divided programmatically into three parts: 1) Study of the pathological impact of obesity on the skeleton, particularly bone and joint health and fracture healing, 2) Elucidating the role of the gut microbiome in posttraumatic and obesity-associated osteoarthritis, and 3) Development of disease-modifying treatments to address joint degeneration in osteoarthritis. Our work spans from bench to bedside, involving basic molecular-cellular biology and microbiology in microbial and cell culture systems, state-of-the-art animal models of disease, and human clinical trials. Our aim is to pursue basic study of skeletal homeostasis and disease, using information gained from that work to develop therapeutic strategies addressing key orthopedic challenges including fracture non-union, osteoporosis, and osteoarthritis.

Publications

• Schott EM, Farnsworth CW, Grier A, Lillis JA, Soniwala S, Dadourian GH, Bell RD, Doolittle ML, Villani DA, Awad H, Ketz JP, Kamal F, Ackert-Bicknell C, Ashton JM, Gill SR, Mooney RA, Zuscik MJ. Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight. 2018 Apr 19;3(8). PubMed PMID: 29669931
• Zingman A, Li H, Sundem L, DeHority B, Geary M, Fussel T, Mooney R, Zuscik M, Elfar J. Shoulder arthritis secondary to rotator cuff tear: A reproducible murine model and histopathologic scoring system. J Orthop Res. 2017 Mar;35(3):506-514. PubMed PMID: 27500994
• Shen J, Wang C, Li D, Xu T, Myers J, Ashton JM, Wang T, Zuscik MJ, McAlinden A, O'Keefe RJ. DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism. JCI Insight. 2017 Jun 15;2(12). PubMed PMID: 28614801
• Farnsworth CW, Schott EM, Jensen SE, Zukoski J, Benvie AM, Refaai MA, Kates SL, Schwarz EM, Zuscik MJ, Gill SR, Mooney RA. Adaptive Upregulation of Clumping Factor A (ClfA) by Staphylococcus aureus in the Obese, Type 2 Diabetic Host Mediates Increased Virulence. Infect Immun. 2017 Jun;85(6). PubMed PMID: 28320836
• Carlson EL, Karuppagounder V, Pinamont WJ, Yoshioka NK, Ahmad A, Schott EM, Le Bleu HK, Zuscik MJ, Elbarbary RA, Kamal F. Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis. Sci Transl Med. 2021 Feb 10;13(580). PubMed PMID: 33568523
• Maynard RD, Villani DA, Schroeder WG, Adams DJ, Zuscik MJ. Surgical Induction of Posttraumatic Osteoarthritis in the Mouse. Methods Mol Biol. 2021;2230:91-103. PubMed PMID: 33197010
• Geary MB, Li H, Zingman A, Ketz J, Zuscik M, De Mesy Bentley KL, Noble M, Elfar JC. Erythropoietin accelerates functional recovery after moderate sciatic nerve crush injury. Muscle Nerve. 2017 Jul;56(1):143-151. PubMed PMID: 28168703
• Le Bleu HK, Kamal FA, Kelly M, Ketz JP, Zuscik MJ, Elbarbary RA. Extraction of high-quality RNA from human articular cartilage. Anal Biochem. 2017 Feb 1;518:134-138. PubMed PMID: 27913164
• Taguchi T, Kotelsky A, Takasugi M, Chang M, Ke Z, Betancourt M, Buckley MR, Zuscik M, Seluanov A, Gorbunova V. Naked mole-rats are extremely resistant to post-traumatic osteoarthritis. Aging Cell. 2020 Nov;19(11):e13255. PubMed PMID: 33112509
• Dar QA, Schott EM, Catheline SE, Maynard RD, Liu Z, Kamal F, Farnsworth CW, Ketz JP, Mooney RA, Hilton MJ, Jonason JH, Prawitt J, Zuscik MJ. Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis. PLoS One. 2017;12(4):e0174705. PubMed PMID: 28384173
• Zhang Y, Sheu TJ, Hoak D, Shen J, Hilton MJ, Zuscik MJ, Jonason JH, O'Keefe RJ. CCN1 Regulates Chondrocyte Maturation and Cartilage Development. J Bone Miner Res. 2016 Mar;31(3):549-59. PubMed PMID: 26363286
• Favazzo LJ, Hendesi H, Villani DA, Soniwala S, Dar QA, Schott EM, Gill SR, Zuscik MJ. The gut microbiome-joint connection: implications in osteoarthritis. Curr Opin Rheumatol. 2020 Jan;32(1):92-101. PubMed PMID: 31724973
• Catheline SE, Hoak D, Chang M, Ketz JP, Hilton MJ, Zuscik MJ, Jonason JH. Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice. J Bone Miner Res. 2019 Sep;34(9):1676-1689. PubMed PMID: 31189030
• Hamada D, Maynard R, Schott E, Drinkwater CJ, Ketz JP, Kates SL, Jonason JH, Hilton MJ, Zuscik MJ, Mooney RA. Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus. Arthritis Rheumatol. 2016 Jun;68(6):1392-402. PubMed PMID: 26713606
• Modrak M, Sundem L, Gupta R, Zuscik MJ, Elfar J. Pharmacological Attenuation of Electrical Effects in a Model of Compression Neuropathy. J Bone Joint Surg Am. 2019 Mar 20;101(6):523-530. PubMed PMID: 30893233
• Tseng KC, Li H, Clark A, Sundem L, Zuscik M, Noble M, Elfar J. 4-Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury. EMBO Mol Med. 2016 Dec;8(12):1409-1420. PubMed PMID: 27861125
• Wang W, Lin X, Xu H, Sun W, Bouta EM, Zuscik MJ, Chen D, Schwarz EM, Xing L. Attenuated Joint Tissue Damage Associated With Improved Synovial Lymphatic Function Following Treatment With Bortezomib in a Mouse Model of Experimental Posttraumatic Osteoarthritis. Arthritis Rheumatol. 2019 Feb;71(2):244-257. PubMed PMID: 30144298
• Farnsworth CW, Schott EM, Benvie AM, Zukoski J, Kates SL, Schwarz EM, Gill SR, Zuscik MJ, Mooney RA. Obesity/type 2 diabetes increases inflammation, periosteal reactive bone formation, and osteolysis during Staphylococcus aureus implant-associated bone infection. J Orthop Res. 2018 Jun;36(6):1614-1623. PubMed PMID: 29227579
• Farnsworth CW, Schott EM, Benvie A, Kates SL, Schwarz EM, Gill SR, Zuscik MJ, Mooney RA. Exacerbated Staphylococcus aureus Foot Infections in Obese/Diabetic Mice Are Associated with Impaired Germinal Center Reactions, Ig Class Switching, and Humoral Immunity. J Immunol. 2018 Jul 15;201(2):560-572. PubMed PMID: 29858265
• Liu Z, Ren Y, Mirando AJ, Wang C, Zuscik MJ, O'Keefe RJ, Hilton MJ. Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance. Osteoarthritis Cartilage. 2016 Apr;24(4):740-51. PubMed PMID: 26522700
• Farnsworth CW, Shehatou CT, Maynard R, Nishitani K, Kates SL, Zuscik MJ, Schwarz EM, Daiss JL, Mooney RA. A humoral immune defect distinguishes the response to Staphylococcus aureus infections in mice with obesity and type 2 diabetes from that in mice with type 1 diabetes. Infect Immun. 2015 Jun;83(6):2264-74. PubMed PMID: 25802056
• Taguchi T, Kotelsky A, Takasugi M, Chang M, Ke Z, Betancourt M, Buckley MR, Zuscik M, Seluanov A, Gorbunova V. Naked mole-rats are extremely resistant to post-traumatic osteoarthritis. Aging Cell. 2020 Nov;19(11):e13255. doi: 10.1111/acel.13255. Epub 2020 Oct 28. PMID: 33112509; PMCID: PMC7681040.
• Shu L, Beier E, Sheu T, Zhang H, Zuscik MJ, Puzas EJ, Boyce BF, Mooney RA, Xing L. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment. Calcif Tissue Int. 2015 Apr;96(4):313-23. PubMed PMID: 25673503
• Mobasheri A, Mahmoudian A, Kalvaityte U, Uzieliene I, Larder CE, Iskandar MM, Kubow S, Hamdan PC, de Almeida CS Jr, Favazzo LJ, van Loon LJC, Emans PJ, Plapler PG, Zuscik MJ. A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis?. Curr Rheumatol Rep. 2021 Oct 30;23(11):78. PubMed PMID: 34716494
• Catheline SE, Bell RD, Oluoch LS, James MN, Escalera-Rivera K, Maynard RD, Chang ME, Dean C, Botto E, Ketz JP, Boyce BF, Zuscik MJ, Jonason JH. IKKß-NF-?B signaling in adult chondrocytes promotes the onset of age-related osteoarthritis in mice. Sci Signal. 2021 Sep 21;14(701):eabf3535. PubMed PMID: 34546791
• Kohn A, Rutkowski TP, Liu Z, Mirando AJ, Zuscik MJ, O'Keefe RJ, Hilton MJ. Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9. Bone Res. 2015;3:15021. PubMed PMID: 26558140
• Beier EE, Sheu TJ, Buckley T, Yukata K, O'Keefe R, Zuscik MJ, Puzas JE. Inhibition of beta-catenin signaling by Pb leads to incomplete fracture healing. J Orthop Res. 2014 Nov;32(11):1397-405. PubMed PMID: 25044211
• Carlson EL, Karuppagounder V, Pinamont WJ, Yoshioka NK, Ahmad A, Schott EM, Le Bleu HK, Zuscik MJ, Elbarbary RA, Kamal F. Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis. Sci Transl Med. 2021 Feb 10;13(580). PubMed PMID: 33568523
• Maynard RD, Villani DA, Schroeder WG, Adams DJ, Zuscik MJ. Surgical Induction of Posttraumatic Osteoarthritis in the Mouse. Methods Mol Biol. 2021;2230:91-103. PubMed PMID: 33197010
• Shi J, Liang Q, Zuscik M, Shen J, Chen D, Xu H, Wang YJ, Chen Y, Wood RW, Li J, Boyce BF, Xing L. Distribution and alteration of lymphatic vessels in knee joints of normal and osteoarthritic mice. Arthritis Rheumatol. 2014 Mar;66(3):657-66. PubMed PMID: 24574226
• Sheu TJ, Zhou W, Fan J, Zhou H, Zuscik MJ, Xie C, Yin G, Berk BC. Decreased BMP2 signal in GIT1 knockout mice slows bone healing. Mol Cell Biochem. 2014 Dec;397(1-2):67-74. PubMed PMID: 25138700
• Brown ML, Yukata K, Farnsworth CW, Chen DG, Awad H, Hilton MJ, O'Keefe RJ, Xing L, Mooney RA, Zuscik MJ. Delayed fracture healing and increased callus adiposity in a C57BL/6J murine model of obesity-associated type 2 diabetes mellitus. PLoS One. 2014;9(6):e99656. PubMed PMID: 24911161
• Thomas SM, Ackert-Bicknell CL, Zuscik MJ, Payne KA. Understanding the Transcriptomic Landscape to Drive New Innovations in Musculoskeletal Regenerative Medicine. Curr Osteoporos Rep. 2022 Apr;20(2):141-152. PubMed PMID: 35156183.
• Payne KA, Favazzo L, Zuscik MJ. Articular Cartilage Biology, Osteoarthritis, Biologics and Stem Cell Therapy. In: Orthopaedic Knowledge Update 14, Eds. Galatz LM and Azar FM. Wolters Kluwer/AAOS.
• David MA, Jones KH, Inzana JA, Zuscik MJ, Awad HA, Mooney RA. Tendon repair is compromised in a high fat diet-induced mouse model of obesity and type 2 diabetes. PLoS One. 2014;9(3):e91234. PubMed PMID: 24658034
• Buckley S, Hamati MC, Hewitt MA, Ackert-Bicknell CL, Zuscik MJ, Metzl J, Moon DK, Hunt KJ. The unique transcriptome of ankle osteoarthritis: a case-control study. AOFAS, submitted.
• Holers VM, Frank RM, Clauw A, Seifert J, Zuscik MJ, Asokan S, Clay MR, Moreland LW, Banda NK. Potential Causal Role of Synovial Complement System Activation in the Development of Post-Traumatic Osteoarthritis after Anterior Cruciate Ligament Injury or Meniscus Tear. Frontiers in Immunology, submitted.
• Yin G, Sheu TJ, Menon P, Pang J, Ho HC, Shi S, Xie C, Smolock E, Yan C, Zuscik MJ, Berk BC. Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting protein-1 (GIT1) knock out mice. PLoS One. 2014;9(2):e89127. PubMed PMID: 24586541
• Hamada D, Sampson ER, Maynard RD, Zuscik MJ. Surgical induction of posttraumatic osteoarthritis in the mouse. Methods Mol Biol. 2014;1130:61-72. PubMed PMID: 24482165
• Mirando AJ, Liu Z, Moore T, Lang A, Kohn A, Osinski AM, O'Keefe RJ, Mooney RA, Zuscik MJ, Hilton MJ. RBP-J?-dependent Notch signaling is required for murine articular cartilage and joint maintenance. Arthritis Rheum. 2013 Oct;65(10):2623-33. PubMed PMID: 23839930
• Inzana JA, Kung M, Shu L, Hamada D, Xing LP, Zuscik MJ, Awad HA, Mooney RA. Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur. Bone. 2013 Nov;57(1):174-83. PubMed PMID: 23954757
• Wang C, Fang L, Niu X, Li T, He Y, Xiao D, Qin H, Lu A, Xing X, Jin H, O'Keefe RJ, Patti GJ, Zuscik MJ, Zhang B, Shen J. Lipid Metabolism Regulates Articular Chondrocyte and Joint Homeostasis. Annals of Rheumatic Disease, in revision.
• Villani DA, Schott EM, Lillis JA, Gill A, Claypool D, Farnsworth CW, Rangel-Moreno J, Hendesi H, Landgrave S, CU Interdisciplinary Joint Biology Consortium, Payne KA, Moreland LW, Zhang F, Anolik JH, Favazzo LJ, Mooney RA, Kuhn KA, Gill SR, Zuscik MJ. Synovial inflammation and B cell infiltration precedes cartilage degeneration in obesity. Journal of Clinical Investigation Insight, submitted.
• Soniwala S, Schott EM, Dar Q-A, Landgrave SH, Hendesi H, Villani DA, Wu A, Thomas SM, Payne KA, Favazzo LJ, Prawitt J, Zuscik MJ. Dietary Supplementation with Hydrolyzed Hyaline Cartilage Mitigates Posttraumatic Osteoarthritis: Potential Role of Shifts in Gut Microbiome. PLOS ONE, submitted.
• MacDonald A, Farnsworth CW, Schott EM, Zhang J, Grier A, Ackert-Bicknell CL, Gill SR, Awad HA, Ketz JP, Mooney RA, Zuscik MJ. Prebiotic alteration of the gut microbiome rescues callus adiposity associated with impaired fracture healing in obesity. Journal of Bone and Mineral Research, submitted.
• Chen T, Hilton MJ, Brown EB, Zuscik MJ, Awad HA. Engineering superficial zone features in tissue engineered cartilage. Biotechnol Bioeng. 2013 May;110(5):1476-86. PubMed PMID: 23239161
• Holers VM, Frank RM, Clauw A, Seifert J, Zuscik M, Asokan S, Striebich C, Clay MR, Moreland LW, Banda NK. Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear. Front Immunol. 2023;14:1146563. PubMed PMID: 37207197
• Villani DA, Eric Schott EM, Myers JA, Zhang J, Gill AL, Claypool D, Farnsworth CW, Rangel-Moreno J, Hendesi H, Landgrave SH, Payne KA, Moreland LW, Anolik JH, Favazzo LJ, Mooney RA, Kuhn KA, Gill SR, and Zuscik MJ. Obesity Related Gut Dysbiosis Promotes Synovial Inflammation and B Cell Infiltration Prior to Osteoarthritic Cartilage Degeneration. In Press, JCI Insight.
• Villani DA, Ishii T, Hendesi H, Landgrave SH, Gill A, Brenner L, Favazzo L, Gill SR, Zuscik MJ. Murine Osteoarthritis Does Not Strongly Impact The Gut Microbiome Community Structure, But Significantly Alters The Functional Output Of Resident Taxa. In Press, Arthritis Research and Therapy.
• Villani DA, Ferreira Ruble A, Landgrave SH, Ishii T, Hendesi H, Zec M, Favazzo L, Gill A, Gill SR, Zuscik MJ. Ablation of Monocyte Chemoattractant Protein 1 from the Colonic Epithelium is Protective in the OA of Obesity. Submitted, Nature Communications.
• Dhillon RS, Xie C, Tyler W, Calvi LM, Awad HA, Zuscik MJ, O'Keefe RJ, Schwarz EM. PTH-enhanced structural allograft healing is associated with decreased angiopoietin-2-mediated arteriogenesis, mast cell accumulation, and fibrosis. J Bone Miner Res. 2013 Mar;28(3):586-97. PubMed PMID: 22991274
• Hendesi H, Soniwala S, Schott E, Villani DA, Dar Q-A, Ferreira Ruble A, Wu A, Gill A, Landgrave SH, Favazzo LJ, Zec M, Gill SR, Prawitt J, Zuscik MJ. Mitigation of Posttraumatic Osteoarthritis via Dietary Supplementation with Hydrolyzed Hyaline Cartilage is Associated with Anti-inflammatory Shifts in the Gut Microbiome. In Press, Nutrients
• Conery M, Pippin JA, Wagley Y, Trang K, Villani DA, Favazzo L, Ackert-Bicknell C, Zuscik MJ, Grant SFA. Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD. Submitted, Nature Genetics.
• Landgrave SH, David MA, Ishii T, Zec T, Godfrey D, Geohring TL, Villani DA, Hendesi H, Ferreira Ruble A, Anderson A, Sanchez A, Payne K, Iyer S, Adams DJ, Favazzo L, Lanske B, Zuscik MJ. Abaloparatide Decelerates Posttraumatic Osteoarthritis Progression in Mice. In Press, Arthritis and Rheumatology.
• Beier EE, Maher JR, Sheu TJ, Cory-Slechta DA, Berger AJ, Zuscik MJ, Puzas JE. Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling. Environ Health Perspect. 2013 Jan;121(1):97-104. PubMed PMID: 23086611
• Gao L, Sheu TJ, Dong Y, Hoak DM, Zuscik MJ, Schwarz EM, Hilton MJ, O'Keefe RJ, Jonason JH. TAK1 regulates SOX9 expression in chondrocytes and is essential for postnatal development of the growth plate and articular cartilages. J Cell Sci. 2013 Dec 15;126(Pt 24):5704-13. PubMed PMID: 24144697
• Holz JD, Beier E, Sheu TJ, Ubayawardena R, Wang M, Sampson ER, Rosier RN, Zuscik M, Puzas JE. Lead induces an osteoarthritis-like phenotype in articular chondrocytes through disruption of TGF-ß signaling. J Orthop Res. 2012 Nov;30(11):1760-6. PubMed PMID: 22517267
• Kohn A, Dong Y, Mirando AJ, Jesse AM, Honjo T, Zuscik MJ, O'Keefe RJ, Hilton MJ. Cartilage-specific RBPj?-dependent and -independent Notch signals regulate cartilage and bone development. Development. 2012 Mar;139(6):1198-212. PubMed PMID: 22354840
• Kung MH, Yukata K, O'Keefe RJ, Zuscik MJ. Aryl hydrocarbon receptor-mediated impairment of chondrogenesis and fracture healing by cigarette smoke and benzo(a)pyrene. J Cell Physiol. 2012 Mar;227(3):1062-70. PubMed PMID: 21567390
• Holers VM, Frank RM, Zuscik M, Keeter C, Scheinman RI, Striebich C, Simberg D, Clay MR, Moreland LW, Banda NK. Decay-Accelerating Factor Differentially Associates With Complement-Mediated Damage in Synovium After Meniscus Tear as Compared to Anterior Cruciate Ligament Injury. Immune Netw. 2024 Apr 29;24(2):e17. doi: 10.4110/in.2024.24.e17. PMID: 38725672; PMCID: PMC11076301.
• Conery M, Pippin JA, Wagley Y, Trang K, Pahl MC, Villani DA, Favazzo LJ, Ackert-Bicknell CL, Zuscik MJ, Katsevich E, Wells AD, Zemel BS, Voight BF, Hankenson KD, Chesi A, Grant SFA. GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density. bioRxiv [Preprint]. 2024 Mar 20:2024.03.19.585778. doi: 10.1101/2024.03.19.585778. PMID: 38562830; PMCID: PMC10983984.
• Honey Hendesi, Dana Godfrey, Ana Ferreira Ruble, Aaron M. Tran, David A. Villani, Samantha H. Landgrave, Hasan A. Nur, Douglas J. Adams, Michael J. Zuscik. Intermittent Fasting Alleviates Obesity-Associated Impairments in Bone Fracture Healing: Exploring the Role of Gut Microbiome. Journal of Orthopaedic Research, In Press.
• Samantha H. Landgrave, Manja M. Zec, Michael A. David, Carson Keeter, Toru Ishii, Sara Higsley, Terrin L. Geohring, Dana A. Godfrey, David A. Villani, Honey Hendesi, Ana Ferreira Ruble, Abigail Anderson, Antonio Sanchez, Karin Payne, Douglas J. Adams, Srividhya Iyer, Lacey J. Favazzo, Beate Lanske, Michael J. Zuscik. Abaloparatide Decelerates Progression of Posttraumatic Osteoarthritis in Mice. Arthritis Research and Therapy, In Press
• Cuicui Wang, Liang Fang, Meng Shi, Xiangfeng Niu, Tiandao Li, Xiaofei Li, Kevin Cho, Yonghua He, Aiwu Lu, Xiaoyun Xing, Jin Liu, Jessica Lukowski, Regis J. O’Keefe, Gary J. Patti, Young Ah Goo, John R. Speakman, Di Chen, Michael J. Zuscik, Bo Zhang, Jie Shen. NFIA regulates articular chondrocyte fatty acid metabolism and joint homeostasis. Science Translational Medicine, In Press.
• David A. Villani, Eric M. Schott, Jacquelyn A. Myers, Jun Zhang, Ann Lindley Gill, David Claypool, Christopher W. Farnsworth, Javier Rangel-Moreno, Honey Hendesi, Samantha H. Landgrave, Karin A. Payne, Larry W. Moreland, Jennifer H. Anolik, Lacey J. Favazzo, Robert A. Mooney, Kristine A. Kuhn, Steven R. Gill, and Michael J. Zuscik. Obesity Related Gut Dysbiosis Promotes Synovial Inflammation and B Cell Infiltration Prior to Osteoarthritic Cartilage Degeneration. JCI Insight, In Press
• Kim KO, Sampson ER, Maynard RD, O'Keefe RJ, Chen D, Drissi H, Rosier RN, Hilton MJ, Zuscik MJ. Ski inhibits TGF-ß/phospho-Smad3 signaling and accelerates hypertrophic differentiation in chondrocytes. J Cell Biochem. 2012 Jun;113(6):2156-66. PubMed PMID: 22461172
• Wang M, Tang D, Shu B, Wang B, Jin H, Hao S, Dresser KA, Shen J, Im HJ, Sampson ER, Rubery PT, Zuscik MJ, Schwarz EM, O'Keefe RJ, Wang Y, Chen D. Conditional activation of ß-catenin signaling in mice leads to severe defects in intervertebral disc tissue. Arthritis Rheum. 2012 Aug;64(8):2611-23. PubMed PMID: 22422036
• Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, Bukata SV, O'Keefe RJ, Awad H, Puzas JE, Rosier RN, Zuscik MJ. Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med. 2011 Sep 21;3(101):101ra93. PubMed PMID: 21937758
• Wang M, Jin H, Tang D, Huang S, Zuscik MJ, Chen D. Smad1 plays an essential role in bone development and postnatal bone formation. Osteoarthritis Cartilage. 2011 Jun;19(6):751-62. PubMed PMID: 21420501
• Jacobson JA, Yanoso-Scholl L, Reynolds DG, Dadali T, Bradica G, Bukata S, Puzas EJ, Zuscik MJ, Rosier R, O'Keefe RJ, Schwarz EM, Awad HA. Teriparatide therapy and beta-tricalcium phosphate enhance scaffold reconstruction of mouse femoral defects. Tissue Eng Part A. 2011 Feb;17(3-4):389-98. PubMed PMID: 20807012
• Sampson ER, Beck CA, Ketz J, Canary KL, Hilton MJ, Awad H, Schwarz EM, Chen D, O'Keefe RJ, Rosier RN, Zuscik MJ. Establishment of an index with increased sensitivity for assessing murine arthritis. J Orthop Res. 2011 Aug;29(8):1145-51. PubMed PMID: 21374709
• Mooney RA, Sampson ER, Lerea J, Rosier RN, Zuscik MJ. High-fat diet accelerates progression of osteoarthritis after meniscal/ligamentous injury. Arthritis Res Ther. 2011;13(6):R198. PubMed PMID: 22152451
• Menon P, Yin G, Smolock EM, Zuscik MJ, Yan C, Berk BC. GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass. J Cell Physiol. 2010 Nov;225(3):777-85. PubMed PMID: 20568227
• Dong Y, Jesse AM, Kohn A, Gunnell LM, Honjo T, Zuscik MJ, O'Keefe RJ, Hilton MJ. RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development. Development. 2010 May;137(9):1461-71. PubMed PMID: 20335360
• Wu Q, Zhu M, Rosier RN, Zuscik MJ, O'Keefe RJ, Chen D. Beta-catenin, cartilage, and osteoarthritis. Ann N Y Acad Sci. 2010 Mar;1192:344-50. PubMed PMID: 20392258
• Yanoso-Scholl L, Jacobson JA, Bradica G, Lerner AL, O'Keefe RJ, Schwarz EM, Zuscik MJ, Awad HA. Evaluation of dense polylactic acid/beta-tricalcium phosphate scaffolds for bone tissue engineering. J Biomed Mater Res A. 2010 Dec 1;95(3):717-26. PubMed PMID: 20725979
• Li TF, Gao L, Sheu TJ, Sampson ER, Flick LM, Konttinen YT, Chen D, Schwarz EM, Zuscik MJ, Jonason JH, O'Keefe RJ. Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: a potential clinical implication for osteoarthritis. Arthritis Rheum. 2010 Aug;62(8):2359-69. PubMed PMID: 20506210
• Clark CA, Li TF, Kim KO, Drissi H, Zuscik MJ, Zhang X, O'Keefe RJ. Prostaglandin E2 inhibits BMP signaling and delays chondrocyte maturation. J Orthop Res. 2009 Jun;27(6):785-92. PubMed PMID: 19023895
• Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C, Rosier RN, O'Keefe RJ, Zuscik M, Chen D. Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res. 2009 Jan;24(1):12-21. PubMed PMID: 18767925
• Naik AA, Xie C, Zuscik MJ, Kingsley P, Schwarz EM, Awad H, Guldberg R, Drissi H, Puzas JE, Boyce B, Zhang X, O'Keefe RJ. Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res. 2009 Feb;24(2):251-64. PubMed PMID: 18847332
• Wu Q, Huang JH, Sampson ER, Kim KO, Zuscik MJ, O'Keefe RJ, Chen D, Rosier RN. Smurf2 induces degradation of GSK-3beta and upregulates beta-catenin in chondrocytes: a potential mechanism for Smurf2-induced degeneration of articular cartilage. Exp Cell Res. 2009 Aug 15;315(14):2386-98. PubMed PMID: 19481076
• Wu Q, Kim KO, Sampson ER, Chen D, Awad H, O'Brien T, Puzas JE, Drissi H, Schwarz EM, O'Keefe RJ, Zuscik MJ, Rosier RN. Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic mice. Arthritis Rheum. 2008 Oct;58(10):3132-44. PubMed PMID: 18821706
• Wu Q, Wang M, Zuscik MJ, Chen D, O'Keefe RJ, Rosier RN. Regulation of embryonic endochondral ossification by Smurf2. J Orthop Res. 2008 May;26(5):704-12. PubMed PMID: 18176945
• Usui M, Xing L, Drissi H, Zuscik M, O'Keefe R, Chen D, Boyce BF. Murine and chicken chondrocytes regulate osteoclastogenesis by producing RANKL in response to BMP2. J Bone Miner Res. 2008 Mar;23(3):314-25. PubMed PMID: 17967138
• Eliseev RA, Dong YF, Sampson E, Zuscik MJ, Schwarz EM, O'Keefe RJ, Rosier RN, Drissi MH. Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis. Oncogene. 2008 Jun 5;27(25):3605-14. PubMed PMID: 18223689
• Zhu M, Chen M, Zuscik M, Wu Q, Wang YJ, Rosier RN, O'Keefe RJ, Chen D. Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum. 2008 Jul;58(7):2053-64. PubMed PMID: 18576323
• Zuscik MJ, Hilton MJ, Zhang X, Chen D, O'Keefe RJ. Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest. 2008 Feb;118(2):429-38. PubMed PMID: 18246193
• Elfar JC, Jacobson JA, Puzas JE, Rosier RN, Zuscik MJ. Erythropoietin accelerates functional recovery after peripheral nerve injury. J Bone Joint Surg Am. 2008 Aug;90(8):1644-53. PubMed PMID: 18676893
• Wu Q, Chen D, Zuscik MJ, O'Keefe RJ, Rosier RN. Overexpression of Smurf2 stimulates endochondral ossification through upregulation of beta-catenin. J Bone Miner Res. 2008 Apr;23(4):552-63. PubMed PMID: 18052755
• Zuscik MJ, Ma L, Buckley T, Puzas JE, Drissi H, Schwarz EM, O'Keefe RJ. Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations. Environ Health Perspect. 2007 Sep;115(9):1276-82. PubMed PMID: 17805416
• Dao DY, Yang X, Chen D, Zuscik M, O'Keefe RJ. Axin1 and Axin2 are regulated by TGF- and mediate cross-talk between TGF- and Wnt signaling pathways. Ann N Y Acad Sci. 2007 Nov;1116:82-99. PubMed PMID: 18083923
• Holz JD, Sheu TJ, Drissi H, Matsuzawa M, Zuscik MJ, Puzas JE. Environmental agents affect skeletal growth and development. Birth Defects Res C Embryo Today. 2007 Mar;81(1):41-50. PubMed PMID: 17539012
• Soung do Y, Dong Y, Wang Y, Zuscik MJ, Schwarz EM, O'Keefe RJ, Drissi H. Runx3/AML2/Cbfa3 regulates early and late chondrocyte differentiation. J Bone Miner Res. 2007 Aug;22(8):1260-70. PubMed PMID: 17488194
• Li TF, Chen D, Wu Q, Chen M, Sheu TJ, Schwarz EM, Drissi H, Zuscik M, O'Keefe RJ. Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes. J Biol Chem. 2006 Jul 28;281(30):21296-21304. PubMed PMID: 16690606
• Eliseev RA, Schwarz EM, Zuscik MJ, O'Keefe RJ, Drissi H, Rosier RN. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NFkappaB. Exp Cell Res. 2006 Jan 1;312(1):40-50. PubMed PMID: 16259979
• Li TF, Darowish M, Zuscik MJ, Chen D, Schwarz EM, Rosier RN, Drissi H, O'Keefe RJ. Smad3-deficient chondrocytes have enhanced BMP signaling and accelerated differentiation. J Bone Miner Res. 2006 Jan;21(1):4-16. PubMed PMID: 16355269
• O'Keefe RJ, Tiyapatanaputi P, Xie C, Li TF, Clark C, Zuscik MJ, Chen D, Drissi H, Schwarz E, Zhang X. COX-2 has a critical role during incorporation of structural bone allografts. Ann N Y Acad Sci. 2006 Apr;1068:532-42. PubMed PMID: 16831949
• Clark CA, Schwarz EM, Zhang X, Ziran NM, Drissi H, O'Keefe RJ, Zuscik MJ. Differential regulation of EP receptor isoforms during chondrogenesis and chondrocyte maturation. Biochem Biophys Res Commun. 2005 Mar 18;328(3):764-76. PubMed PMID: 15694412
• Carmouche JJ, Puzas JE, Zhang X, Tiyapatanaputi P, Cory-Slechta DA, Gelein R, Zuscik M, Rosier RN, Boyce BF, O'Keefe RJ, Schwarz EM. Lead exposure inhibits fracture healing and is associated with increased chondrogenesis, delay in cartilage mineralization, and a decrease in osteoprogenitor frequency. Environ Health Perspect. 2005 Jun;113(6):749-55. PubMed PMID: 15929899
• Drissi H, Zuscik M, Rosier R, O'Keefe R. Transcriptional regulation of chondrocyte maturation: potential involvement of transcription factors in OA pathogenesis. Mol Aspects Med. 2005 Jun;26(3):169-79. PubMed PMID: 15811433
• Wei X, Zhang X, Zuscik MJ, Drissi MH, Schwarz EM, O'Keefe RJ. Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner after stimulation with titanium particles. J Bone Miner Res. 2005 Jul;20(7):1136-48. PubMed PMID: 15940366
• Eliseev RA, Zuscik MJ, Schwarz EM, O'Keefe RJ, Drissi H, Rosier RN. Increased radiation-induced apoptosis of Saos2 cells via inhibition of NFkappaB: a role for c-Jun N-terminal kinase. J Cell Biochem. 2005 Dec 15;96(6):1262-73. PubMed PMID: 16167336
• Dong Y, Drissi H, Chen M, Chen D, Zuscik MJ, Schwarz EM, O'Keefe RJ. Wnt-mediated regulation of chondrocyte maturation: modulation by TGF-beta. J Cell Biochem. 2005 Aug 1;95(5):1057-68. PubMed PMID: 15962307
• Li TF, Dong Y, Ionescu AM, Rosier RN, Zuscik MJ, Schwarz EM, O'Keefe RJ, Drissi H. Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway. Exp Cell Res. 2004 Sep 10;299(1):128-36. PubMed PMID: 15302580
• Li TF, Zuscik MJ, Ionescu AM, Zhang X, Rosier RN, Schwarz EM, Drissi H, O'Keefe RJ. PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling. Exp Cell Res. 2004 Oct 15;300(1):159-69. PubMed PMID: 15383323
• Zuscik MJ, Baden JF, Wu Q, Sheu TJ, Schwarz EM, Drissi H, O'Keefe RJ, Puzas JE, Rosier RN. 5-azacytidine alters TGF-beta and BMP signaling and induces maturation in articular chondrocytes. J Cell Biochem. 2004 May 15;92(2):316-31. PubMed PMID: 15108358
• Zhang X, Ziran N, Goater JJ, Schwarz EM, Puzas JE, Rosier RN, Zuscik M, Drissi H, O'Keefe RJ. Primary murine limb bud mesenchymal cells in long-term culture complete chondrocyte differentiation: TGF-beta delays hypertrophy and PGE2 inhibits terminal differentiation. Bone. 2004 May;34(5):809-17. PubMed PMID: 15121012
• Ionescu AM, Drissi H, Schwarz EM, Kato M, Puzas JE, McCance DJ, Rosier RN, Zuscik MJ, O'Keefe RJ. CREB Cooperates with BMP-stimulated Smad signaling to enhance transcription of the Smad6 promoter. J Cell Physiol. 2004 Mar;198(3):428-40. PubMed PMID: 14755548
• Ferguson CM, Schwarz EM, Puzas JE, Zuscik MJ, Drissi H, O'Keefe RJ. Transforming growth factor-beta1 induced alteration of skeletal morphogenesis in vivo. J Orthop Res. 2004 Jul;22(4):687-96. PubMed PMID: 15183422
• Zhang D, Schwarz EM, Rosier RN, Zuscik MJ, Puzas JE, O'Keefe RJ. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J Bone Miner Res. 2003 Sep;18(9):1593-604. PubMed PMID: 12968668
• Li X, Ionescu AM, Schwarz EM, Zhang X, Drissi H, Puzas JE, Rosier RN, Zuscik MJ, O'Keefe RJ. Smad6 is induced by BMP-2 and modulates chondrocyte differentiation. J Orthop Res. 2003 Sep;21(5):908-13. PubMed PMID: 12919880
• Li X, Schwarz EM, Zuscik MJ, Rosier RN, Ionescu AM, Puzas JE, Drissi H, Sheu TJ, O'Keefe RJ. Retinoic acid stimulates chondrocyte differentiation and enhances bone morphogenetic protein effects through induction of Smad1 and Smad5. Endocrinology. 2003 Jun;144(6):2514-23. PubMed PMID: 12746314
• Zuscik MJ, Rosier RN, Schwarz EM. Altered negative regulation of transforming growth factor beta signaling in scleroderma: potential involvement of SMURF2 in disease. Arthritis Rheum. 2003 Jul;48(7):1779-80. PubMed PMID: 12847669
• Sheu TJ, Schwarz EM, Martinez DA, O'Keefe RJ, Rosier RN, Zuscik MJ, Puzas JE. A phage display technique identifies a novel regulator of cell differentiation. J Biol Chem. 2003 Jan 3;278(1):438-43. PubMed PMID: 12403789
• Yun J, Zuscik MJ, Gonzalez-Cabrera P, McCune DF, Ross SA, Gaivin R, Piascik MT, Perez DM. Gene expression profiling of alpha(1b)-adrenergic receptor-induced cardiac hypertrophy by oligonucleotide arrays. Cardiovasc Res. 2003 Feb;57(2):443-55. PubMed PMID: 12566117
• Drissi MH, Li X, Sheu TJ, Zuscik MJ, Schwarz EM, Puzas JE, Rosier RN, O'Keefe RJ. Runx2/Cbfa1 stimulation by retinoic acid is potentiated by BMP2 signaling through interaction with Smad1 on the collagen X promoter in chondrocytes. J Cell Biochem. 2003 Dec 15;90(6):1287-98. PubMed PMID: 14635200
• Ionescu AM, Schwarz EM, Zuscik MJ, Drissi H, Puzas JE, Rosier RN, O'Keefe RJ. ATF-2 cooperates with Smad3 to mediate TGF-beta effects on chondrocyte maturation. Exp Cell Res. 2003 Aug 1;288(1):198-207. PubMed PMID: 12878171
• Zuscik MJ, O'Keefe RJ, Gunter TE, Puzas JE, Schwarz EM, Rosier RN. Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A. J Orthop Res. 2002 Sep;20(5):1079-90. PubMed PMID: 12382976
• Kunieda T, Zuscik MJ, Boongird A, Perez DM, Lüders HO, Najm IM. Systemic overexpression of the alpha 1B-adrenergic receptor in mice: an animal model of epilepsy. Epilepsia. 2002 Nov;43(11):1324-9. PubMed PMID: 12423381
• Papay R, Zuscik MJ, Ross SA, Yun J, McCune DF, Gonzalez-Cabrera P, Gaivin R, Drazba J, Perez DM. Mice expressing the alpha(1B)-adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation. J Neurochem. 2002 Nov;83(3):623-34. PubMed PMID: 12390524
• Zuscik MJ, D'Souza M, Ionescu AM, Gunter KK, Gunter TE, O'Keefe RJ, Schwarz EM, Puzas JE, Rosier RN. Growth plate chondrocyte maturation is regulated by basal intracellular calcium. Exp Cell Res. 2002 Jun 10;276(2):310-9. PubMed PMID: 12027460
• Zuscik MJ, Pateder DB, Puzas JE, Schwarz EM, Rosier RN, O'Keefe RJ. Lead alters parathyroid hormone-related peptide and transforming growth factor-beta1 effects and AP-1 and NF-kappaB signaling in chondrocytes. J Orthop Res. 2002 Jul;20(4):811-8. PubMed PMID: 12168672
• Waugh DJ, Gaivin RJ, Zuscik MJ, Gonzalez-Cabrera P, Ross SA, Yun J, Perez DM. Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1-adrenergic receptor antagonist binding. Imidazoline agonists bind like antagonists. J Biol Chem. 2001 Jul 6;276(27):25366-71. PubMed PMID: 11331292
• Zuscik MJ, Chalothorn D, Hellard D, Deighan C, McGee A, Daly CJ, Waugh DJ, Ross SA, Gaivin RJ, Morehead AJ, Thomas JD, Plow EF, McGrath JC, Piascik MT, Perez DM. Hypotension, autonomic failure, and cardiac hypertrophy in transgenic mice overexpressing the alpha 1B-adrenergic receptor. J Biol Chem. 2001 Apr 27;276(17):13738-43. PubMed PMID: 11278430
• Zuscik MJ, Sands S, Ross SA, Waugh DJ, Gaivin RJ, Morilak D, Perez DM. Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy. Nat Med. 2000 Dec;6(12):1388-94. PubMed PMID: 11100125
• Waugh DJ, Zhao MM, Zuscik MJ, Perez DM. Novel aromatic residues in transmembrane domains IV and V involved in agonist binding at alpha(1a)-adrenergic receptors. J Biol Chem. 2000 Apr 21;275(16):11698-705. PubMed PMID: 10766790
• Perez DM, Zuscik MJ. Solution-phase library screening for identification of rare adrenergic receptor clones. Methods Mol Biol. 2000;126:91-116. PubMed PMID: 10685404
• Perez DM, Zuscik MJ. Polymerase chain reaction screening of genomic libraries for adrenergic receptor genes. Methods Mol Biol. 2000;126:73-89. PubMed PMID: 10685403
• Zuscik MJ, Piascik MT, Perez DM. Cloning, cell-type specificity, and regulatory function of the mouse alpha(1B)-adrenergic receptor promoter. Mol Pharmacol. 1999 Dec;56(6):1288-97. PubMed PMID: 10570057
• Zuscik MJ, Porter JE, Gaivin R, Perez DM. Identification of a conserved switch residue responsible for selective constitutive activation of the beta2-adrenergic receptor. J Biol Chem. 1998 Feb 6;273(6):3401-7. PubMed PMID: 9452461
• Zuscik MJ, Gunter TE, Puzas JE, Rosier RN. Characterization of voltage-sensitive calcium channels in growth plate chondrocytes. Biochem Biophys Res Commun. 1997 May 19;234(2):432-8. PubMed PMID: 9177288
• Martinez DA, Zuscik MJ, Ishibe M, Rosier RN, Romano PR, Cushing JE, Puzas JE. Identification of functional insulin-like growth factor-II/mannose-6-phosphate receptors in isolated bone cells. J Cell Biochem. 1995 Oct;59(2):246-57. PubMed PMID: 8904318
• Zuscik MJ, Puzas JE, Rosier RN, Gunter KK, Gunter TE. Cyclic-AMP-dependent protein kinase activity is not required by parathyroid hormone to stimulate phosphoinositide signaling in chondrocytes but is required to transduce the hormone's proliferative effect. Arch Biochem Biophys. 1994 Dec;315(2):352-61. PubMed PMID: 7986078
• Zuscik MJ, Gunter TE, Rosier RN, Gunter KK, Puzas JE. Activation of phosphoinositide metabolism by parathyroid hormone in growth plate chondrocytes. Cell Calcium. 1994 Aug;16(2):112-22. PubMed PMID: 7982262
• Gunter KK, Zuscik MJ, Gunter TE. The Na(+)-independent Ca2+ efflux mechanism of liver mitochondria is not a passive Ca2+/2H+ exchanger. J Biol Chem. 1991 Nov 15;266(32):21640-8. PubMed PMID: 1939193
• Gunter TE, Zuscik MJ, Puzas JE, Gunter KK, Rosier RN. Cytosolic free calcium concentrations in avian growth plate chondrocytes. Cell Calcium. 1990 Aug;11(7):445-57. PubMed PMID: 2272080

Professional Memberships

• Orthopaedic Research Society, Member
• American Society for Bone and Mineral Research, Member
• Osteoarthritis Research Society International, Member