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Updated: Aug 31, 2025

Author Spotlight: Advancements in Cell and Tissue Engineering for Tendon Repair
Published on: March 1, 2024
RSPO2 defines a distinct undifferentiated progenitor in the tendon/ligament and suppresses ectopic ossification
Naohiro Tachibana1, Ryota Chijimatsu2, Hiroyuki Okada3
1Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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 (+) 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 κB. Rspo2 cells may contribute to tendon/ligament homeostasis under pathogenic conditions.
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