Project description:Ectopic endochondral ossification in the tendon/ligament is caused by repetitive mechanical overload or inflammation. Tendon stem/progenitor cells (TSPCs) contribute to tissue repair and lubrication by producing proteoglycan 4 (Prg4). However, the mechanisms of ectopic ossification and association of TSPCs are not yet known. Here, we investigated the characteristics of Prg4-positive (+) cells and identified that R-spondin 2 (RSPO2), a WNT activator, is specifically expressed in a distinct Prg4+ TSPC cluster. The Rspo2+ cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. RSPO2 expression levels in patients with ossification of the posterior longitudinal ligament were lower than those in spondylosis patients, and RSPO2 protein suppressed chondrogenic differentiation of human ligament cells. RSPO2 was induced by inflammatory stimulation and mechanical loading via nuclear factor-kappa B (NF-κB). Rspo2+ cells may contribute to tendon/ligament homeostasis by suppressing chondrogenic differentiation.
Project description:We have compared the gene expression profile of post-natal 1 day and 7 day rat Achilles tendons. Post-natal 1 day and 7 day rat Achilles tendons were collected. Each sample contains at least two individuals. Total RNA was extracted and fragmented biotin-tagged cRNA was hybridized to Rat Genome 230 2.0 Array.
Project description:Tamoxifen time course in two independent R26-CreERT2 Adar1fl/+ and two independent R26-CreERT2 Adar1fl/E861A immortalised myeloid cell lines.
Project description:The purpose of this project is to determine changes in proteins and signaling pathways in injured tendons of C57BL/6j and MRL/MpJ mice. The MRL.MpJ mice have been reported to have a strong repair ability compared to that of C57BL/6j mice. Identifying signaling pathways in MRL/MpJ tendons that are distinct from C57BL/6j tendons will help us understand the molecular mechanisms underlying the better healing ability of MRL/MpJ mice. The samples include normal and injured Achilles tendons 4 weeks after tenotomy surgery obtained from male and female C57BL/6j and MRL/MpJ. The Achilles injury surgery was performed at 12 weeks of age. Normal tendons were obtained age, sex and strain-matched mice without surgery. The collected normal and inured tendons were subjected to proteomics.