Age-dependent role of BMP13 in cartilage homeostasis

Purpose Age is a primary risk factor for osteoarthritis (OA) development, which is characterized by articular cartilage destruction. However, age-related changes leading to altered cartilage homeostasis and increased susceptibility to OA development need further elucidation. Thus, this study aimed to assess bone morphogenetic protein (BMP)13 age-dependent effects on cartilage extracellular matrix (ECM) homeostasis.Methods Both juvenile and adult cartilage explants were treated with BMP13 and both transcriptomic and biochemical changes were assessed to determine effects on ECM homeostasis. Dorsomorphin and U0126 were utilized to inhibit the SMAD1/5/8 and ERK1/2 pathways, respectively, to investigate their role in mediating BMP13 effects.Results Exogenous BMP13 upregulated MMP3 in adult and, to a much lesser extent, juvenile cartilage. BMP13 also upregulated NOS2 and MMP13 in adult cartilage. At the biochemical level, BMP13 induced catabolic responses only in adult cartilage, reducing sGAG content and upregulating matrix metalloproteinase (MMP) activity and nitric oxide (NO) production. In juvenile cartilage, BMP13 activation of the SMAD1/5/8 pathway resulted in low levels of MMP activity. Conversely, in adult cartilage, BMP13 activation of SMAD1/5/8 induced NO, while BMP13 activation of ERK1/2 signaling upregulated total MMP activity.Conclusions We provide novel findings that age leads to differential activation of BMP13 signaling pathways that regulate pro-inflammatory and catabolic mediators in adult cartilage. These findings suggest a potential age-dependent mechanism in response to BMP13 that promotes alterations in ECM homeostasis and could increase susceptibility to OA development.