Epidemiological studies have shown that high bone mineral density (BMD) is associated with an increased risk of osteoarthritis (OA), but the causality of this relationship remains unclear. Both bone mass and OA have been associated with the WNT signaling pathway in genetic studies, there is thus an interest in studying molecular partners of the WNT signaling pathway and OA. Female mice overexpressing WNT16 in osteoblasts (Obl-Wnt16 mice) have an increased bone mass. We aimed to evaluate if the high bone mass in Obl-Wnt16 mice leads to a more severe experimental OA development than in WT control mice. We induced experimental OA in female Obl-Wnt16 and WT control mice by destabilizing the medial meniscus (DMM). The Obl-Wnt16 mice displayed thicker medial and lateral subchondral bone plates as well as increased subchondral trabecular bone volume/tissue volume (BV/TV) but un-altered thickness of articular cartilage compared to WT mice. After DMM surgery, there was no difference in OA severity in the articular cartilage in the knee joint between the Obl-Wnt16 and WT mice. Both the Obl-Wnt16 and WT mice developed osteophytes in the DMM-operated tibia to a similar extent. We conclude that although the Obl-Wnt16 female mice have a high subchondral bone mass due to increased WNT signaling, they do not exhibit a more severe OA phenotype than their WT controls. This demonstrates that high bone mass does not result in an increased risk of OA per se.

流行病学研究表明，高的骨矿物质密度（BMD）与骨关节炎（OA）的风险增加有关，但这种关系的因果关系仍不清楚。在遗传研究中，骨量和OA均与WNT信号通路相关，因此有兴趣研究WNT信号通路和OA的分子伴侣。成骨细胞中过表达WNT16的雌性小鼠（Obl-Wnt16小鼠）的骨量增加。我们旨在评估Obl-Wnt16小鼠中的高骨量是否导致比WT对照小鼠更严重的实验性OA发育。我们通过使内侧半月板（DMM）不稳定来诱导雌性Obl-Wnt16和WT对照小鼠的实验性OA 。该OBL-WNT16与野生型小鼠相比，小鼠表现出更厚的内侧和外侧软骨下骨板，以及软骨下小梁骨体积/组织体积（BV / TV）增加，但关节软骨厚度未改变。DMM手术后，在Obl-Wnt16和WT小鼠之间，膝关节的关节软骨的OA严重程度没有差异。两者OBL-WNT16和WT小鼠开发在DMM操作胫骨骨赘到相似的程度。我们得出的结论是，尽管Obl-Wnt16雌性小鼠由于WNT信号增强而具有较高的软骨下骨量，但它们的WT表型没有比其WT对照更为严重。这表明高骨量本身不会增加OA的风险。