AI Article Synopsis
- Joint contracture is a permanent mobility disorder caused by factors like trauma and aging, primarily due to joint capsule fibrosis, but the exact molecular reasons are still unclear.
- A mouse model study revealed that increased levels of the protein periostin (POSTN) in joint capsules are linked to irreversible contractures, with significant fibrosis observed.
- Treatment with POSTN-neutralizing antibodies showed promise in reducing contracture severity, highlighting POSTN as a potential target for future therapies to address joint contracture.
Article Abstract
Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFP ; Postn mice and chimeric mice with Col1a2-GFP ; tdTomato bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.
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| http://dx.doi.org/10.1096/fj.202201598R | DOI Listing |
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