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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 comprehensive 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 analyses of clinical information and retrieved tissues from patients. We believe that the combined information obtained from these models will improve our understanding of the underlying mechanisms that lead to disease onset and progression, and will allow us to test targeted approaches with potential therapeutic application.

We use this information to:

  • Study OA as a whole joint disorder, with emphasis in understanding 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

  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.

Principal Investigator

Miguel Otero, PhD
Assistant Scientist and Laboratory Director, Orthopedic Soft Tissue Research Program, HSS
Co-Director, Derfner Foundation Precision Medicine Laboratory, HSS
Assistant Professor of Cell and Developmental Biology in Orthopedic Surgery, WCMC

Current Lab Members

Maxwell Konnaris, BS, PostBac Researcher
Samantha Lessard, BA, Senior Research Technician
Laura Moore, MD, PhD, Clinical Fellow, Sports Medicine
Brennan Rourke, BS, PostBac Researcher
Purva Singh, PhD, Research Associate

Previous Lab Members

Dhabia Al-Merekhi, Medical Student Research Award Program, WCM-Qatar
Bijan Dehghani, Research Intern
Marjan Khan, Research Technician
Tyler Khilnani, Summer Intern (co-mentor: Dr. Maher)
Christine Kim, HSS-Columbia Summer Intern
Martin Schonk, PostBac Researcher (co-mentor: Dr. Rodeo)
Bradley Schussel, Summer Intern
Mengying Wang, PhD Student
Elisabeth Wondimu, PhD Candidate (co-mentor: Dr. Goldring)
Xiaoning (Jenny) Yuan, Senior Resident (co-mentor: Dr. Rodeo)
Habib Zahir, Research Technician

HSS Collaborators

Franck Barrat, PhD
Tony Chen, PhD
Mary B. Goldring, PhD
Meghan Kirksey, MD, PhD
Matthew Koff, PhD
Suzanne Maher, PhD
Bella Mehta, MBBS, MS, MD
Alessandra Pernis, MD
Scott Rodeo, MD
Peter Sculco, MD
Timothy Wright, PhD

HSS Center for Regenerative Medicine
Complex Joint Reconstruction Center - TKAF Consortium
Derfner Foundation Precision Medicine Laboratory

Recent Publications

  • Singh P, Wang M, Mukherjee P, Lessard SG, Pannellini T, Carballo CB, Rodeo SA, Goldring MB, Otero M. Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis. Sci Rep. 2021 Oct www.nature.com/articles/s41598-021-00269-8
  • Monibi FA, Pannellini T, Croen B, Otero M, Warren R, Rodeo SA. Targeted transcriptomic analyses of RNA isolated from formalin-fixed and paraffin-embedded human menisci. J Orthop Res. 2021 Aug 9. doi: 10.1002/jor.25153. Epub ahead of print. PMID: 34370349
  • Ziemian SN, Witkowski AM, Wright TM, Otero M, van der Meulen MCH. Early inhibition of subchondral bone remodeling slows load-induced posttraumatic osteoarthritis development in mice. J Bone Miner Res. 2021 Jun 22. doi: 10.1002/jbmr.4397. Epub ahead of print. PMID: 34155675.
  • Zahir H, Dehghani B, Yuan X, Chinenov Y, Kim C, Burge A, Bandhari R, Nemirov D, Fava P, Moley P, Potter H, Nguyen J, Halpern B, Donlin L, Ivashkiv L, Rodeo S, Otero M. In vitro responses to platelet-rich plasma are associated with variable clinical outcomes in patients with knee osteoarthritis. Sci Rep. 2021 Jun 1;11(1):11493. doi: 10.1038/s41598-021-90174-x. PMID: 34075069; PMCID: PMC8169703
  • Culley KL, Singh P, Lessard S, Wang M, Rourke B, Goldring MB, Otero M. Mouse Models of Osteoarthritis: Surgical Model of Post-traumatic Osteoarthritis Induced by Destabilization of the Medial Meniscus. Methods Mol Biol. 2021;2221:223-260. doi: 10.1007/978-1-0716-0989-7_14. PMID: 32979207.
  • Xia Y, Sokhi UK, Bell RD, Pannellini T, Turajane K, Niu Y, Frye L, Chao M, Ayturk U, Otero M, Bostrom M, Oliver D, Yang X, Ivashkiv LB. Immune and repair responses in joint tissues and lymph nodes after knee arthroplasty surgery in mice. J Bone Miner Res. 2021 Jun 2. doi: 10.1002/jbmr.4381. Epub ahead of print. PMID: 34076292.
  • Monibi FA, Pannellini T, Otero M, Warren RF, Rodeo SA. Histologic and molecular features in pathologic human menisci from knees with and without osteoarthritis. J Orthop Res. 2021 Apr 1. doi: 10.1002/jor.25047. Epub ahead of print. PMID: 33792974.
  • Krzyzanowska AK, Frawley RJ, Damle S, Chen T, Otero M, Cunningham ME. Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1. Sci Rep. 2021 Apr 15;11(1):8271. doi: 10.1038/s41598-021-87665-2. PMID: 33859255; PMCID: PMC8050288.
  • Wang M, Lessard S, Singh P, Pannellini T, Chen T, Rourke B, Chowdhury L, Craveiro V, Sculco P, van der Meulen M, and Otero M. Knee fibrosis is associated with the development of osteoarthritis in a murine model of tibial compression. J Orthop Res. 2020; 1– 11. https://doi.org/10.1002/jor.24815
  • Fang R, Haxaire C, Otero M, Lessard S, Weskamp G, McIlwain DR, Mak TW, Lichtenthaler SF, Blobel CP. Role of iRhoms 1 and 2 in Endochondral Ossification. Int J Mol Sci. 2020 Nov 19;21(22):8732. doi: 10.3390/ijms21228732. PMID: 33227998; PMCID: PMC7699240
  • Singh P, Lessard SG, Mukherjee P, Rourke B, Otero M. Changes in DNA methylation accompany changes in gene expression during chondrocyte hypertrophic differentiation in vitro. Ann N Y Acad Sci. 2020 Sep 25. doi: 10.1111/nyas.14494. Epub ahead of print. PMID: 32978775.
  • Luna M, Guss JD, Vasquez-Bolanos LS, Alepuz AJ, Dornevil S, Strong J, Alabi D, Shi Q, Pannellini T, Otero M, Brito IL, van der Meulen MCH, Goldring SR, Hernandez CJ. Obesity and Load-induced Posttraumatic Osteoarthritis in the Absence of Fracture or Surgical Trauma. J Orthop Res. 2020 Jul 13. doi: 10.1002/jor.24799. Epub ahead of print. PMID: 32658313.
  • Giovanni Trisolino, Marta Favero, Dante Dallari, Enrico Tassinari, Francesco Traina, Miguel Otero, Steven R. Goldring, Mary B. Goldring, Chiara Carubbi, Roberta Ramonda, Stefano Stilli, Brunella Grigolo & Eleonora Olivotto. Labral calcification plays a key role in hip pain and symptoms in femoroacetabular impingement. J Orthop Surg Res 15, 86 (2020). https://doi.org/10.1186/s13018-020-01610-z
  • Eliasberg CD, Wada S, Carballo CB, Nakagawa Y, Nemirov DA, Bhandari R, Otero M, Deng XH, Rodeo SA. Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model. J Orthop Res. 2019 Dec;37(12):2575-2582. doi: 10.1002/jor.24434. Epub 2019 Aug 13. PMID: 31378986.
  • Culley KL, Lessard SG, Green JD, Quinn J, Chang J, Khilnani T, Wondimu EB, Dragomir CL, Marcu KB, Goldring MB, Otero M. Inducible knockout of CHUK/IKKα in adult chondrocytes reduces progression of cartilage degradation in a surgical model of osteoarthritis. Sci Rep. 2019 Jun 20;9(1):8905. doi: 10.1038/s41598-019-45334-5. PMID: 31222033 https://www.ncbi.nlm.nih.gov/pubmed/31222033
  • Holyoak DT, Chlebek K, Kim MJ, Wright TM, Otero M, van der Meulen MCH. Low-level cyclic tibial compression attenuates osteoarthritis progression after joint injury in mice. Osteoarthritis Cartilage. 2019 Jun pii: S1063-4584(19)31094-5. doi: 10.1016/j.joca.2019.06.005. [Epub ahead of print]. PMID: 31265883 https://www.ncbi.nlm.nih.gov/pubmed/31265883
  • Singh P, Marcu KB, Goldring MB, Otero M. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy. Ann N Y Acad Sci. 2019 Apr;1442(1):17-34. doi: 10.1111/nyas.13930. Epub 2018 Jul Review. PMID: 30008181 https://www.ncbi.nlm.nih.gov/pubmed/30008181
  • He Y, Zhang Y, Zhang D, Zhang M, Wang M, Jiang Z, Otero M, Chen J. 3-morpholinosydnonimine (SIN-1)-induced oxidative stress leads to necrosis in hypertrophic chondrocytes in vitro. Biomed Pharmacother. 2018 Oct; 106:1696-1704. doi: 10.1016/j.biopha.2018.07.128. Epub 2018 Jul 30. PMID: 30119244
  • Liu H, Fang Q, Wang M, Wang W, Zhang M, Zhang D, He Y, Zhang Y, Wang H, Otero M, Ma T, Chen J. FGF8 and FGFR3 are up-regulated in hypertrophic chondrocytes: Association with chondrocyte death in deep zone of Kashin-Beck disease. Biochem Biophys Res Commun. 2018 Jun 2;500(2):184-190. doi: 10.1016/j.bbrc.2018.04.023. Epub 2018 Apr 17. PMID: 29626475
  • Wondimu EB, Culley KL, Quinn J, Chang J, Dragomir CL, Plumb DA, Goldring MB, Otero M. Elf3 Contributes to Cartilage Degradation in vivo in a Surgical Model of Post-Traumatic Osteoarthritis. Sci Rep. 2018 Apr 24;8(1):6438. doi: 10.1038/s41598-018-24695-3. PMID: 29691435
  • Conde J, Otero M, Scotece M, Abella V, Gómez R, López V, Pino J, Mera A, Goldring MB, Gualillo O. E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage. Cell Physiol Biochem. 2018;45(6):2401-2410. doi: 10.1159/000488227. Epub 2018 Mar 13. PMID: 29550824.

For a complete publication list, please see My Bibliography

Funding Sources

The Nancy Dickerson Whitehead Research Fellowship
Anna-Maria and Stephen Kellen Foundation
Ambrose Monell Foundation
Orthopaedic Research and Education Foundation (PI: S Rodeo)
HSS Surgeon-In-Chief Research Grant
The Stavros Niarchos Foundation, Complex Joint Reconstruction Center
The STARR Foundation (PI: V Tabar)
HSS Research Institute COVID-19 Initiativ

Past Support:
NIH/NIA 1 R21 AG049980-01A1
Feldstein Medical Foundation
Weill Cornell Clinical and Translational Science Center