Gene expression and histological studies of articular chondrocytes in cam-type femoroacetabular impingement demonstrates chronic and sustained inflammation and age related abnormal extracellular matrix

Liang, Haixiang; Neufeld, Eric V.; Schaffler, Benjamin C.; Mashura, Michael; Matzko, Chelsea; Grande, Daniel; Bharam, Srino

doi:10.1016/j.jcjp.2021.100011

Cited by 2 publications

(4 citation statements)

References 34 publications

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“…While we observed increased expression of these markers in the OA compared to the total FAI cohort on the sequencing arm of this study, subsequent validation with qRT‐PCR found similar expression between high‐grade FAI and osteoarthritic cartilage, suggesting that expression of inflammatory markers increases as FAI progresses towards OA. These findings were supported in a recent study by Liang and colleagues who found differences in COL2A1, ACAN, and MMP3 immunostaining between early and late‐stage FAI samples 18 . Taken together, these results suggest that as the degenerative processes of FAI become more advanced the articular cartilage expression profile parallels that of osteoarthritic cartilage.…”

Section: Discussionsupporting

confidence: 80%

“…Several studies have evaluated the expression of inflammatory markers isolated from pathologic tissues in FAI and hip OA (Table 1). [7][8][9][10][11][12][13] In a preliminary study of articular cartilage harvested during cam resection for FAI compared to articular cartilage from osteoarthritic hips, Hashimoto et al reported increased expression of inflammatory mediators and markers of cartilage turnover (IL8, ADAMTS4, ACAN). 7 In a subsequent study, Chinzei et al 7 confirmed increased expression of inflammatory markers in FAI cartilage compared to OA, while OA labral and synovial samples had higher levels of inflammation compared to FAI.…”

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confidence: 99%

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

Kuhns

Reuter

Hansen

et al. 2022

Journal Orthopaedic Research

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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 wholegenome 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:Camtype FAI has a strong clinical association with hip OA; however, the cellular pathophysiology of disease progression remains poorly understood. Several previous

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

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

Kuhns

Reuter

Hansen

et al. 2022

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…These findings were supported in a recent study by Liang and colleagues who found differences in COL2A1, ACAN, and MMP3 immunostaining between early and late-stage FAI samples. 12 Taken together, these results suggest that there are both etiologic and temporal factors impacting gene expression between FAI and osteoarthritic cartilage, and as the degenerative processes of FAI become more advanced the articular cartilage expression profile parallels that of osteoarthritic cartilage.…”

Section: Discussionmentioning

confidence: 63%

“…Differential expression for previously identified markers in FAI and OA [6][7][8][9][10][11][12]. *indicates increased expression in OA compared to FAI.…”

mentioning

confidence: 99%

Whole-Genome RNA Sequencing of Femoral Head Impingement Cartilage Identifies FGF18 As A Biomarker in Hip Osteoarthritis Progression

Kuhns

Reuter

Hansen

et al. 2022

Preprint

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IntroductionThe natural history of Femoroacetabular Impingement (FAI) has been clinically associated with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain unclear. The goal of the study was to investigate differences in transcriptomic profiles of the cartilage from FAI and hip OA patients using whole-genome RNA sequencing.MethodsThirty-seven patients were included in the study with 20 diagnosed with FAI undergoing arthroscopic treatment and 15 diagnosed with hip OA undergoing total hip arthroplasty (THA). Cartilage samples were obtained intraoperatively over the femoral head-neck junction for both FAI and OA cohorts. Whole-genome RNA sequencing was performed on 10 gender-matched patients in the FAI and OA cohorts with the remaining samples used for histopathologic analysis using the Osteoarthritis Research Society International (OARSI) grading system and qRT-PCR validation. Target validation was further confirmed with immunohistochemical staining for FGF18 on FAI and OA cartilage samples.ResultsWe identified a total of 3,531 Differentially Expressed Genes (DEGs) between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. qRT-PCR 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 (OARSI grades 1-2) compared to FAI samples with severe cartilage damage or OA cartilage (OARSI grade 4-6). Immunohistochemical evaluation identified increased FGF18 staining in OARSI grade 1-2 FAI samples compared to OARSI grade 5-6 FAI and OA samples.ConclusionsRNA sequencing of cartilage of FAI and hip OA patients identified a negative association of FGF18 expression levels with cartilage damage severity, suggesting that FGF18 may be used as a marker for hip OA progression. Future evaluation of FGF18 signaling as well as other markers in early OA may yield further insight into disease prevention and treatment.

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Gene expression and histological studies of articular chondrocytes in cam-type femoroacetabular impingement demonstrates chronic and sustained inflammation and age related abnormal extracellular matrix

Cited by 2 publications

References 34 publications

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

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

Whole-Genome RNA Sequencing of Femoral Head Impingement Cartilage Identifies FGF18 As A Biomarker in Hip Osteoarthritis Progression

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