RSPO2 defines a distinct undifferentiated progenitor in the tendon/ligament and suppresses ectopic ossification

Naohiro Tachibana, Ryota Chijimatsu, Hiroyuki Okada, Takeshi Oichi, Yuki Taniguchi, Yuji Maenohara, Junya Miyahara, Hisatoshi Ishikura, Yasuhide Iwanaga, Yusuke Arino, Kosei Nagata, Hideki Nakamoto, So Kato, Toru Doi, Yoshitaka Matsubayashi, Yasushi Oshima, Asuka Terashima, Yasunori Omata, Fumiko Yano, Shingo MaedaShiro Ikegawa, Masahide Seki, Yutaka Suzuki, Sakae Tanaka, Taku Saito

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)eabn2138
JournalScience Advances
Volume8
Issue number33
DOIs
Publication statusPublished - Aug 19 2022

ASJC Scopus subject areas

  • General

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