Abstract
ABSTRACTArticular cartilage (AC) is essential for body movement, but is highly susceptible to degenerative diseases and has poor self-repair capacity. To improve current subpar regenerative treatment, developmental mechanisms of AC should be clarified and, specifically, how postnatal multi-zone organization is acquired. Primary cilia are cell surface organelles crucial for mammalian tissue morphogenesis and while the importance of chondrocyte primary cilia is well appreciated their specific roles in postnatal AC morphogenesis remain unclear. To explore these mechanisms, we used a murine conditional loss-of-function approach (Ift88-flox) targeting joint-lineage progenitors (Gdf5Cre) and monitored postnatal knee AC development. Joint formation and growth up to juvenile stages were largely unaffected, however mature AC (aged 2 months) exhibited disorganized extracellular matrix, decreased aggrecan and collagen II due to reduced gene expression (not increased catabolism), and marked reduction of AC modulus by 30-50%. In addition, we discovered the surprising findings that tidemark patterning was severely disrupted and accompanied alterations in hedgehog signaling that were also dependent on regional load-bearing functions of AC. Interestingly, Prg4 expression was also increased in those loaded sites. Together, our data provide evidence that primary cilia orchestrate postnatal AC morphogenesis, dictating tidemark topography, zonal matrix composition and mechanical load responses.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献