Revealing a Natural Model of Pre-Osteoarthritis of the Hip Through Study of Femoroacetabular Impingement.

Autor:	Pascual-Garrido C; Adult Reconstruction-Adolescent and Young Adult Hip Service, Department of Orthopaedic Surgery, School of Medicine, Washington University, St. Louis, MO, USA., Kikuchi K; Adult Reconstruction-Adolescent and Young Adult Hip Service, Department of Orthopaedic Surgery, School of Medicine, Washington University, St. Louis, MO, USA., Clohisy JC; Adult Reconstruction-Adolescent and Young Adult Hip Service, Department of Orthopaedic Surgery, School of Medicine, Washington University, St. Louis, MO, USA., O'Keefe RJ; Adult Reconstruction-Adolescent and Young Adult Hip Service, Department of Orthopaedic Surgery, School of Medicine, Washington University, St. Louis, MO, USA., Kamenaga T; Adult Reconstruction-Adolescent and Young Adult Hip Service, Department of Orthopaedic Surgery, School of Medicine, Washington University, St. Louis, MO, USA.
Jazyk:	angličtina
Zdroj:	HSS journal : the musculoskeletal journal of Hospital for Special Surgery [HSS J] 2023 Nov; Vol. 19 (4), pp. 434-441. Date of Electronic Publication: 2023 Aug 09.
DOI:	10.1177/15563316231190084
Abstrakt:	Femoroacetabular impingement (FAI) is considered the mechanical cause of hip osteoarthritis (OA). Surgical intervention involves labrum repair and osteochondroplasty to remove the impingement, alleviating symptoms. Nevertheless, some patients progress to hip OA after surgery, indicating that factors other than mechanical abnormality are contributing to hip OA progression. This review article discusses our laboratory's studies on hip FAI and OA, undertaken to identify key molecular players in the progression of hip OA. Transcriptome analysis identified peroxisome proliferator activated receptor gamma (PPARγ) as a crucial molecule in early hip OA. PPARγ, widely expressed in chondrocytes, has a protective role in preventing OA, but its true mechanism remains unknown. We observed a dysregulation of DNA methyltransferase (DNMT) in the progression of hip OA, with high expression of DNMT1 and 3A and downregulation of DNMT3B. Moreover, we established that DNMT3A is the main molecule that is binding to PPARγ promoter CpG area, and hypermethylation of this area occurs during disease progression. This suggests that epigenetic changes are a main mechanism that regulates PPARγ expression. Finally, we developed a novel rabbit model of hip FAI and OA and are currently performing studies to validate our small-animal model to human FAI. Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Cecilia Pascual-Garrido, MD, PhD, reports relationships with the National Institutes of Health, Orthopedic Research and Education Foundation, ARVIS, Zed View Lexi 3D Developing Software, and the National Football League Musculoskeletal Committee. John C. Clohisy, MD, reports relationships with the Department of Defense–USAMRAA, Zimmer Biomet, Wolters Kluwer Health, Microport Orthopedics, Hip Society, International Society for Hip Arthroscopy, International Hip Society, ANCHOR Fund, and Curing Hip Disease Fund. Regis J. O’Keefe, MD, PhD, reports relationships with the National Institutes of Health, Fate Therapeutics, Loma Linda University, University of Vermont, MiMedx Group, University Health Network of the University of Toronto Advisory Board, and Indiana Center for Musculoskeletal Health, and he holds a patent (DNA methyltransferases for the treatment and prevention of arthritis, #US-10123983-B2). The other authors declare no potential conflicts of interest. (© The Author(s) 2023.)
Databáze:	MEDLINE
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