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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 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.

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.

Osteoarthritis (OA) of the hip is a common and debilitating painful joint disease. A growing body of evidence suggests that there may be an association between periarticular myotendinous pathology and the development of hip OA. Thus, we hypothesized that a murine model of hip OA could be achieved through selective injury of the abductor complex around the hip. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free, active movement until sacrifice at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining (IHC) of the femoral head articular cartilage were performed, along with μCT analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significant OA severity with loss of Type II Collagen staining compared to sham control mice at 20 weeks post-surgery, comparable MMPI13 expression was observed between injury and sham groups. No significant differences in subchondral bone were found on μCT after 20 weeks following injury. Our study suggests a link between abductor dysfunction and the development of hip OA, which are common pathomorphologies encountered in routine orthopaedic clinical practice. Further, this novel animal model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.

Background Episode-based bundled payments for total knee arthroplasty emphasize cost-effective patient-centered care. Understanding patients' perceptions of components of the total knee arthroplasty care episode is critical to achieving this care. This study investigated patient preferences for components of the total knee arthroplasty care episode. Methods Best-worst scaling was used to analyze patient preferences for components of the total knee arthroplasty care episode. Participants were selected from patients presenting to 2 orthopaedic clinics with chronic knee pain. They were presented with descriptions of 17 attributes before completing a best-worst scaling exercise. Attribute importance was determined using hierarchical Bayesian estimation. Latent class analysis was used to evaluate varying preference profiles. Results One hundred and seventy-four patients completed the survey, and 117 patients (67%) were female. The mean age was 62.71 years. Participants placed the highest value on surgeon factors, including level of experience, satisfaction rating, and complication rates. Latent class analysis provided a 4-segment model of the population. Conclusions This study demonstrated differences in patient preferences for the components of a total knee arthroplasty care episode and characterized distinct preference profiles among patient subsets. Stakeholders can use this information to focus efforts and policy on high-value components and to potentially create customized bundles guided by preference profiles. Clinical relevance This study is clinically relevant because the patient preferences identified here may help providers to design customized bundles for total knee arthroplasty care.