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:RNA sequencing of FACS sorted microglia isolated from brain tissue of WT, Hexb-tdTomato, Hexb-CreERT2 and Hexb-KO mice was performed to test for potential differences in gene expression caused by the knock-in of tdTomato and CreERT2 into the Hexb locus.
Project description:RNA sequencing of FACS sorted microglia isolated from brain tissue of WT, Hexb-tdTomato, Hexb-CreERT2 and Hexb-KO mice was performed to test for potential differences in gene expression caused by the knock-in of tdTomato and CreERT2 into the Hexb locus.
Project description:RNA sequencing of FACS sorted microglia isolated from brain tissue of WT, Hexb-tdTomato, Hexb-CreERT2 and Hexb-KO mice was performed to test for potential differences in gene expression caused by the knock-in of tdTomato and CreERT2 into the Hexb locus.
Project description:We report RNA sequencing data from the Achilles, patellar, supraspinatus, and forepaw flexor tendons of adult male rats in the Sprague-Dawley
Project description:We report RNA sequencing data from the Achilles, patellar, supraspinatus, and forepaw flexor tendons of adult male mice in the C57Bl/6 background.
Project description:Tendon is a highly aligned connective tissue, in which the macro-structure consists of collagen-rich fascicles surrounded by interfascicular matrix (IFM). In a series of recent studies in equine tissue, we have demonstrated specialisation of tendon composition, structure and mechanics to achieve the tendon’s functional requirements, specifically reporting extensive specialisation of the IFM region in the energy storing superficial digital flexor tendon. We have also demonstrated loss of functional specialisms with ageing, leading to a hypothesised new paradigm for tendinopathy, focused on the importance of the IFM. However, to date, there have been no studies focused on structure-function specialisation or the IFM in functionally distinct human tendons. Here, we compare the positional anterior tibialis tendon and energy storing Achilles tendon, performing a detailed analysis of the composition and mechanical properties of both fascicle and IFM regions, to test the hypothesis that the IFM in the energy storing Achilles tendon has specialised composition and mechanical properties, and that these specialisations are lost with ageing. We demonstrate that the IFM is specialised in the energy storing Achilles tendon, with greater elasticity and fatigue resistance than in the positional anterior tibialis tendon. While there were few age-related alterations in mechanics, we did identify age-related alterations in the IFM proteome of the Achilles tendon specifically, which is predicted to be regulated by TGF-beta signalling and may be responsible for the trend towards decreased fatigue resistance observed in the Achilles IFM with ageing.