Whole-genome RNA sequencing identifies distinct transcriptomic profiles in impingement cartilage between patients with femoroacetabular impingement and hip osteoarthritis.

Autor: Kuhns BD; Center for Regenerative and Personalized Medicine, Steadman-Philippon Research Institute, Vail, Colorado, USA., Reuter JM; Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA., Hansen VL; Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA., Soles GL; Department of Orthopedic Surgery, University of California Davis Health System, Sacramento, California, USA., Jonason JH; Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA., Ackert-Bicknell CL; Colorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Wu CL; Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA., Giordano BD; Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA.
Jazyk: angličtina
Zdroj: Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2023 Jul; Vol. 41 (7), pp. 1517-1530. Date of Electronic Publication: 2022 Dec 04.
DOI: 10.1002/jor.25485
Abstrakt: Femoroacetabular impingement (FAI) has a strong clinical association with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain poorly understood. The purpose of this study is to use whole-genome RNA sequencing to identify and subsequently validate differentially expressed genes (DEGs) in femoral head articular cartilage samples from patients with FAI and hip OA secondary to FAI. Thirty-seven patients were included in the study with whole-genome RNA sequencing performed on 10 gender-matched patients in the FAI and OA cohorts and the remaining specimens were used for validation analyses. We identified a total of 3531 DEGs between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. Quantitative reverse transcription-polymerase chain reaction validation confirmed increased expression of FGF18 and WNT16 in the FAI samples, while there was increased expression of MMP13 and ADAMTS4 in the OA samples. Expression levels of FGF18 and WNT16 were also higher in FAI samples with mild cartilage damage compared to FAI samples with severe cartilage damage or OA cartilage. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. We independently validated the results of the sequencing analysis and found increased expression of anabolic markers in patients with FAI and minimal histologic cartilage damage, suggesting that anabolic signaling may be increased in early FAI with a transition to catabolic and inflammatory gene expression as FAI progresses towards more severe hip OA. Clinical significance:Cam-type FAI has a strong clinical association with hip OA; however, the cellular pathophysiology of disease progression remains poorly understood. Several previous studies have demonstrated increased expression of inflammatory markers in FAI cartilage samples, suggesting the involvement of these inflammatory pathways in the disease progression. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. In addition to differences in inflammatory gene expression, we also identified differential expression in multiple pathways involved in hip OA progression.
(© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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