Laboratory of Molecular Osteoarthritis Research

Our goal is to understand the altered signaling pathways that prompt joint tissue disruption in osteoarthritis (OA).

We are using state-of-the-art approaches to define knee OA patient subtypes, assess how different joint tissues contribute to OA disease, and test non-surgical therapies. Our models span cell-based approaches, in vivo systems, and studies that integrate clinical information with multimodal analyses of clinical samples.

We use this information to:

  • Study OA as a whole joint disorder, with emphasis in understanding pain mechanisms, and the contribution of the infrapatellar fat pad to disease onset and progression.
  • Define patient subtypes aiming to develop predictive platforms to identify good candidates for non-surgical treatments or patients who are at risk of developing poor surgical outcomes.
  • Uncover distinct cellular and molecular signatures associated with structural damage and knee fibrosis and stiffness, and target these signatures to modify disease progression.
Areas of Investigation

Areas of Investigation

  1. Integration of clinical, histological, ultrasound, genomic, and proteomic datasets to identify clinically-relevant knee OA subtypes with prognostic value.
  2. Defining the cellular, genomic, and epigenomic changes that contribute to the development of knee fibrosis and OA disease, and to arthrofibrosis after total knee arthroplasty (TKA)
  3. Investigating non-surgical regenerative medicine approaches to treat knee OA and prevent the development of post-traumatic OA

The goal of the Otero lab is to define the altered signaling pathways that prompt to the joint tissue disruption in osteoarthritis (OA), and to develop and utilize in vivo and in vitro systems designed to dissect complex transcriptional regulatory networks that are abnormally dysregulated in OA. We are particularly interested in understanding how altered immune/inflammatory pathways that are abnormally activated in response to injurious biochemical and biochemical stimuli lead to long-lasting (epigenetic) alterations in different joint cells, which in turn drive knee fibrosis and stiffness, and cartilage degradation. Ultimately, we aim to improve our understanding of the underlying disease mechanisms to develop approaches with potential therapeutic application.

Laboratory Personnel

Laboratory Personnel

Principal Investigator

Miguel Otero, PhD
Director, HSS Molecular Histopathology Core Laboratory
Associate Director for Translational Research, HSS Center for Regenerative Medicine  
Co-Director, Derfner Foundation Precision Medicine Laboratory, HSS
Assistant Professor of Cell and Developmental Biology in Orthopaedic Surgery, WCMC

Current Lab Members

HSS Collaborators

Publications and Funding Sources

Publications and Funding Sources

Recent Publications

  • Cruz-Almeida Y, Mehta B, Haelterman NA, Johnson AJ, Heiting C, Ernberg M, Orange D, Lotz M, Boccanfuso J, Smith SB, Pela M, Boline J, Otero M, Allen K, Perez D, Donnelly C, Almarza A, Olmer M, Balkhi H, Wagenaar J, Martone M; RE- JOIN Consortium Investigators. Clinical and biobehavioral phenotypic assessments and data harmonization for the RE-JOIN research consortium: Recommendations for common data element selection. Neurobiol Pain. 2024 Aug 22;16:100163. doi: 10.1016/j.ynpai.2024.100163. (Review)
  • Bell RD, Brendel M, Konnaris MA, Xiang J, Otero M, Fontana MA, Bai Z; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium; Krenitsky DM, Meednu N, Rangel-Moreno J, Scheel-Toellner D, Carr H, Nayar S, McMurray J, DiCarlo E, Anolik JH, Donlin LT, Orange DE, Kenney HM, Schwarz EM, Filer A, Ivashkiv LB, Wang F. Automated multi- scale computational pathotyping (AMSCP) of inflamed synovial tissue. Nat Commun. 2024 Aug 29;15(1):7503. doi: 10.1038/s41467-024-51012-6. 
  • Antoinette AY, Ziemian SN, Brown AR, Hudson EB, Chlebek C, Wright TM, Goldring SR, Goldring MB, Otero M, van der Meulen MCH. PTH treatment before cyclic joint loading improves cartilage health and attenuates load-induced osteoarthritis development in mice. Sci Adv. 2024 Apr 19;10(16):eadk8402. doi: 10.1126/sciadv.adk8402.  
  • Chen N, Wei X, Zhao G, Jia Z, Fu X, Jiang H, Xu X, Zhao Z, Singh P, Lessard S, Otero M, Goldring MB, Goldring SR, Wang D. Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis. Nanomedicine. 2024 Apr;57:102735. doi: 10.1016/j.nano.2024.102735.  
  • Jenkins D, Phalke S, Bell R, Lessard S, Gupta S, Youssef M, Tam K, Nocon A, Rivera-Correa J, Wright T, Sculco T, Otero M, Pernis AB, Sculco P. Adaptive immune responses in patients requiring revision after total knee arthroplasty. J Orthop Res. 2023 May;41(5):984-993. doi: 10.1002/jor.25445.  
  • Mehta B, Goodman S, DiCarlo E, Jannat-Khah D, Gibbons JAB, Otero M, Donlin L, Pannellini T, Robinson WH, Sculco P, Figgie M, Rodriguez J, Kirschmann JM, Thompson J, Slater D, Frezza D, Xu Z, Wang F, Orange DE. Machine learning identification of thresholds to discriminate osteoarthritis and rheumatoid arthritis synovial inflammation. Arthritis Res Ther. 2023 Mar 2;25(1):31. doi: 10.1186/s13075-023-03008-8. PubMed PMID: 36864474; PubMed Central PMCID: PMC9979511.

For a complete publication list, please see My Bibliography

Funding Sources

  • Arthritis Foundation 
  • NIH/NIAMS UC2 AR 082186 (PI: Anne Marie Malfait, subaward site PI: Bella Mehta)
  • The Marietta Voglis Osteoarthritis Fund
  • The Nancy Dickerson Whitehead Research Fellowship
  • Anna-Maria and Stephen Kellen Foundation
  • Derfner Foundation
  • Ambrose Monell Foundation
  • Orthopaedic Research and Education Foundation (PI: Laura Moore and Scott Rodeo)
  • The Stavros Niarchos Foundation, Complex Joint Reconstruction Center

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