RSPO2 defines a distinct undifferentiated progenitor in the tendon/ligament and suppresses ectopic ossification.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35984875.
- Also identified by DOI 10.1126/sciadv.abn2138 and PMC identifier 9390986.
- Licence recorded as CC BY-NC.
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Abstract
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 some express lubricin [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 (<sup>+</sup>) cells and identified that R-spondin 2 (RSPO2), a WNT activator, is specifically expressed in a distinct <i>Prg4<sup>+</sup></i> TSPC cluster. The <i>Rspo2</i><sup>+</sup> cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. <i>RSPO2</i> 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 κB. <i>Rspo2<sup>+</sup></i> cells may contribute to tendon/ligament homeostasis under pathogenic conditions.