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.
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DOI：
10.1002/jor.25485
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发表时间：
2023-07
影响因子：
2.8
通讯作者：
Giordano, Brian D. D.
中科院分区：
文献类型：
--
作者：
Kuhns, Benjamin D. D.;Reuter, John M. M.;Hansen, Victoria L. L.;Soles, Gillian L. L.;Jonason, Jennifer H. H.;Ackert-Bicknell, Cheryl L. L.;Wu, Chia-Lung;Giordano, Brian D. D.
股骨髋臼撞击（FAI）与髋关节骨关节炎（OA）的发生有很强的临床相关性;然而，从局灶性撞击到整体关节退变的病理生物学机制仍然知之甚少。本研究的目的是使用全基因组RNA测序，以确定和随后验证差异表达的基因（DEG）在股骨头关节软骨样本与FAI和髋关节OA继发于FAI的患者。37例患者被纳入研究，对FAI和OA队列中10例性别匹配的患者进行全基因组RNA测序，其余标本用于验证分析。我们在FAI和OA队列中共鉴定了3531个DEG，这些DEG具有涉及典型OA途径的多个基因靶点。定量逆转录-聚合酶链反应验证证实FAI样本中FGF 18和WNT 16的表达增加，而OA样本中MMP 13和ADAMTS 4的表达增加。与具有严重软骨损伤或OA软骨的FAI样本相比，具有轻度软骨损伤的FAI样本中FGF 18和WNT 16的表达水平也更高。我们的研究进一步扩展了关于FAI和髋关节OA患者之间软骨中不同基因重编程的知识。我们独立验证了测序分析的结果，发现FAI和最小组织学软骨损伤患者的合成代谢标志物表达增加，表明合成代谢信号可能在早期FAI中增加，随着FAI向更严重的髋关节OA进展，合成代谢和炎症基因表达转变。临床意义：CAM型FAI与髋关节OA有很强的临床相关性;然而，对疾病进展的细胞病理生理学仍知之甚少。先前的几项研究已经证明FAI软骨样本中炎症标志物的表达增加，表明这些炎症途径参与了疾病进展。我们的研究进一步扩展了关于FAI和髋关节OA患者之间软骨中不同基因重编程的知识。除了炎症基因表达的差异外，我们还确定了髋关节OA进展中涉及的多种途径的差异表达。
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.
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DOI：
10.1084/jem.182.6.2097
发表时间：
1995-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Amin AR;Di Cesare PE;Vyas P;Attur M;Tzeng E;Billiar TR;Stuchin SA;Abramson SB
通讯作者：
Abramson SB
影响因子：
1.9
作者：
Liu, Jie;Hao, Yangquan;Lu, Chao
通讯作者：
Lu, Chao
DOI：
10.1177/0363546513499308
发表时间：
2013-11
期刊：
The American journal of sports medicine
影响因子：
--
作者：
Bedi A;Lynch EB;Sibilsky Enselman ER;Davis ME;Dewolf PD;Makki TA;Kelly BT;Larson CM;Henning PT;Mendias CL
通讯作者：
Mendias CL
影响因子：
4.9
作者：
Leijten JC;Bos SD;Landman EB;Georgi N;Jahr H;Meulenbelt I;Post JN;van Blitterswijk CA;Karperien M
通讯作者：
Karperien M
影响因子：
2.6
作者：
Gao G;Wu R;Liu R;Wang J;Ao Y;Xu Y
通讯作者：
Xu Y