An increased prevalence of osteoarthritis (OA) in post-menopausal women has led to the suggestion that hormonal factors may play a role in the pathogenesis. This study aims to examine if undergoing a hysterectomy, both with retention and removal of ovaries, predisposes women to OA and secondly if the development is influenced by hormone replacement therapy (HRT). Statistical shape modelling (SSM) is a method of image analysis allowing for detection of subtle shape variation described by landmark points. Through the generation of linearly independent modes of variation, each image can be described in terms of numerical scores. 149 radiographs from female participants of the Osteoarthritis Initiative (OAI) were examined to compare hip morphology in those who had undergone hysterectomies compared to controls. No differences were observed in BMI, age, height or weight between groups. ANOVA and Games-Howell post-hoc analysis showed that modes 3 and 5 were statistically significant. Lower mode 3 scores were associated with hysterectomy (p=0.019), with narrowing of the femoral neck and increased acetabular coverage. Lower mode 5 scores were associated with hysterectomy and oophorectomy (p=0.049), displaying reduced coverage of the femoral head, superolateral migration of the femoral head and larger greater trochanter. No associations were observed between HRT use and OA. The subtle morphologic features of hip OA present in only hysterectomised women suggests undergoing a hysterectomy may be a predisposing factor and a clinical consideration. The use of HRT was not observed to influence the development of OA and thus cannot be suggested as a protective measure.
Proliferation of synovial Mesenchymal Stromal/Stem Cells (MSCs) leads to synovial hyperplasia (SH) following Joint Surface Injury (JSI). Uncontrolled Yap activity causes tissue overgrowth due to modulation of MSC proliferation. We hypothesised that YAP plays a role in SH following JSI. A spatiotemporal analysis of Yap expression was performed using the JSI model in C57Bl/6 mice. Synovial samples from patients were similarly analysed. Gdf5-Cre;Yap1fl/fl;Tom mice were created to determine the effect YAP1 knockout in Gdf5 lineage cells on SH after JSI. In patients, Yap expression was upregulated in activated synovium, including a subset of CD55 positive fibroblast-like synoviocytes in the synovial lining (SL). Cells staining positive for the proliferation marker Ki67 expressed active YAP. In mice, Yap was highly expressed in injured knee joint synovium compared to controls. Yap mRNA levels at 2 (p<0.05) and 8 days (p<0.001) after injury were increased. Conditional Yap1 knockout in Gdf5 progeny cells prevented hyperplasia of synovial lining (SL) after JSI. Cellularity was significantly decreased in the SL but not in the sub-lining of injured Yap1 knockout- compared to control mice. The percentage of cells in synovium that were Tom+ increased in response to JSI in control and haplo-insufficient but not in YAP1 knockout mice (p<0.05). Modulation of YAP and proliferation of MSCs in the synovium after JSI provides a system to study the role of SH after trauma in re-establishing joint homeostasis and is a potential novel therapeutic target for the treatment of post traumatic OA.
