ObjectivesSynovium is acutely affected following joint trauma and contributes to post-traumatic osteoarthritis (PTOA) progression. Little is known about discrete cell types and molecular mechanisms in PTOA synovium. We aimed to describe synovial cell populations and their dynamics in PTOA, with a focus on fibroblasts. We also sought to define mechanisms of synovial Wnt/β-catenin signalling, given its emerging importance in arthritis.MethodsWe subjected mice to non-invasive anterior cruciate ligament rupture as a model of human joint injury. We performed single-cell RNA-sequencing to assess synovial cell populations, subjected Wnt-GFP reporter mice to joint injury to study Wnt-active cells, and performed intra-articular injections of the Wnt agonist R-spondin 2 (Rspo2) to assess whether gain of function induced pathologies characteristic of PTOA. Lastly, we used cultured fibroblasts, macrophages and chondrocytes to study how Rspo2 orchestrates crosstalk between joint cell types.ResultsWe uncovered seven distinct functional subsets of synovial fibroblasts in healthy and injured synovium, and defined their temporal dynamics in early and established PTOA. Wnt/β-catenin signalling was overactive in PTOA synovium, and Rspo2 was strongly induced after injury and secreted exclusively by Prg4hi lining fibroblasts. Trajectory analyses predicted that Prg4hi lining fibroblasts arise from a pool of Dpp4+ mesenchymal progenitors in synovium, with SOX5 identified as a potential regulator of this emergence. We also showed that Rspo2 orchestrated pathological crosstalk between synovial fibroblasts, macrophages and chondrocytes.ConclusionsSynovial fibroblasts assume distinct functional identities during PTOA in mice, and Prg4hi lining fibroblasts secrete Rspo2 that may drive pathological joint crosstalk after injury.
Introduction: While there are multiple barriers that may discourage women from choosing a career in orthopaedic surgery, one area of concern is pursuing pregnancy during residency training. This study's primary purpose was to determine the most prominent barriers to pursuing pregnancy during orthopaedic surgery residency. Methods: A 63-item survey designed to evaluate multiple aspects of childbearing during orthopaedic surgery residency was distributed through email and a targeted Facebook platform to female orthopaedic surgeons and orthopaedic trainees in the United States. Given the study design, statistics were largely descriptive in nature. Multivariate logistic regression was also used to determine independent factors associated with professional dissatisfaction as it related to pregnancy during orthopaedic residency. Results: A total of 328 women responded to the survey. The 3 most prominent barriers to pursuing pregnancy during orthopaedic residency were concerns about the ability to balance clinical and maternal duties (67%), fear of how the resident would be viewed by those in the program (60%), and being unable to ensure optimal prenatal and postpartum care for the mother and child given an unpredictable schedule (38%). On univariate analysis of those who reported ‡1 pregnancy during residency (n = 71), maternity leave £6 weeks was statistically associated with "revisiting career choice" (p = 0.02) and "lack of resources and support" (p = 0.01). Conclusion:The results raise concern that qualified female applicants may be deterred from the field of orthopaedics given perceived difficulties associated with pregnancy as a resident. If policies are created to support women who desire to have children during residency, more women may be encouraged to pursue a career in orthopaedic surgery. Level of Evidence: V Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A447).
The aim of the study was to investigate the relationship between socioeconomic status and pain reduction from epidural steroid injections for lumbar radiculopathy. Methods: The retrospective cohort consisted of patients undergoing epidural steroid injection for lumbar radiculopathy (n = 544). Numeric Pain Rating Scale was measured at baseline and 2 wks after epidural steroid injection. Socioeconomic status was estimated using median family income in patients' ZIP code. Linear and mixed models examined demographic and clinical differences in pain before and after injection and whether family income moderated the effect. Results: Majority of patients were White (72.4%), female (56.4%), engaged in physical activity (68.2%), and underwent unilateral, transforaminal epidural steroid injection (86.0% and 92.1%, respectively). Non-White patients and those who did not engage in physical activity had higher baseline pain ( P < 0.05). Lower socioeconomic status was associated with higher baseline pain (β = 0.06 per $10,000, P = 0.01). Patients with lower socioeconomic status experienced larger improvement in pain after epidural steroid injection: −1.56 units for patients in the 10th percentile of family income versus −0.81 for 90th percentile. Being a current smoker was associated with higher pain (β = 0.76, P = 0.03) and engaging in structured physical activity with less pain (β = −0.07 P < 0.01). Conclusions: Lower socioeconomic status was independently associated with higher pain alleviation after controlling for other potentially influential demographics. Modifiable lifestyle factors may be a target of potential intervention.
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