Tachibana Naohiro, Chijimatsu Ryota, Okada Hiroyuki, Oichi Takeshi, Taniguchi Yuki, Maenohara Yuji, Miyahara Junya, Ishikura Hisatoshi, Iwanaga Yasuhide, Arino Yusuke, Nagata Kosei, Nakamoto Hideki, Kato So, Doi Toru, Matsubayashi Yoshitaka, Oshima Yasushi, Terashima Asuka, Omata Yasunori, Yano Fumiko, Maeda Shingo, Ikegawa Shiro, Seki Masahide, Suzuki Yutaka, Tanaka Sakae, Saito Taku
Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Bone and Cartilage Regenerative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Sci Adv. 2022 Aug 19;8(33):eabn2138. doi: 10.1126/sciadv.abn2138.
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 TSPC cluster. The cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. 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. cells may contribute to tendon/ligament homeostasis under pathogenic conditions.
肌腱/韧带中的异位软骨内成骨是由重复性机械过载或炎症引起的。肌腱干/祖细胞（TSPCs）有助于组织修复，并且一些细胞表达润滑素[蛋白聚糖4（PRG4）]。然而，异位骨化的机制以及TSPCs的关联尚不清楚。在此，我们研究了Prg4阳性（）细胞的特征，并确定WNT激活剂R-spondin 2（RSPO2）在一个独特的TSPC簇中特异性表达。该簇的特征是大多未分化，并且RSPO2过表达通过抑制软骨形成分化在小鼠跟腱穿刺模型中抑制异位骨化。后纵韧带骨化患者中的表达水平低于脊柱病患者，并且RSPO2蛋白抑制人韧带细胞的软骨形成分化。RSPO2由炎症刺激和通过核因子κB的机械负荷诱导。细胞可能在致病条件下有助于肌腱/韧带的稳态。
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