PTHrP suppresses BMP2-induced osteochondral differentiation and preserves cartilage phenotype in mesenchymal stem cells via inactivating PI3K-AKT signaling.

Authors

Shengqiang Gao, Piao Zhao, Tingting Du, Yu Ye, Shengwen Cheng, Senrui Liu, Chengcheng Du, Tong-Chuan He, Wei Huang, Zhenglin Zhu, Wei Xu, Junyi Liao

Published in

Genes & diseases. Volume 14. Issue 2. Pages 102273. Epub Jun 05, 2026.

Abstract

Bone morphogenetic protein 2 (BMP2) has the potential to drive multipotent mesenchymal stem cells (MSCs) to undergo chondral-osteogenic (including hypertrophic chondrocyte) differentiation. Parathyroid hormone-related protein (PTHrP) plays an essential role in fetal endochondral ossification, although persistent PTHrP stimulation leads to postnatal bone loss. Here, we investigated the effects of PTHrP on BMP2-induced endochondral ossification through hypertrophic chondrocyte differentiation of MSCs. We found that silencing PTHrP expression inhibited BMP2-induced chondrogenic, hypertrophic, and osteogenic differentiation of MSCs, while overexpression of PTHrP promoted BMP2-induced chondrogenic differentiation of MSCs and suppressed BMP2-induced hypertrophic differentiation of MSCs. Using stem cell implantation studies in athymic nude mice, we demonstrated that while MSCs with silenced PTHrP expression exhibited significantly reduced endochondral ossification of subcutaneous cartilage, overexpression of PTHrP promoted the growth of subcutaneous cartilage while significantly delaying ossification, leading to the preservation of cartilage phenotype. Mechanistically, we showed that exogenous PTHrP promoted BMP2-induced chondrogenic differentiation of MSCs by up-regulating Sox9 expression and inactivating PI3K-AKT signaling. Collectively, our findings strongly suggest that PTHrP may play an important role in mediating BMP2-induced chondral-osteogenic differentiation of MSCs by inactivating PI3K-AKT signaling, indicating that PTHrP may be exploited for endochondral cartilage-bone tissue engineering.

PMID:
42926813
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.