Constitutive activation of TGF-β receptor type I promotes cortical and cancellous bone formation in adult mice
Issued Date
2026-03-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-105031575924
Journal Title
Plos One
Volume
21
Issue
3 March
Rights Holder(s)
SCOPUS
Bibliographic Citation
Plos One Vol.21 No.3 March (2026)
Suggested Citation
Chotipinit T., Toejing P., Phetkong C., Sridurongrit S., Leelahavanichkul A., Charles J.F., Lotinun S. Constitutive activation of TGF-β receptor type I promotes cortical and cancellous bone formation in adult mice. Plos One Vol.21 No.3 March (2026). doi:10.1371/journal.pone.0344279 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115612
Title
Constitutive activation of TGF-β receptor type I promotes cortical and cancellous bone formation in adult mice
Corresponding Author(s)
Other Contributor(s)
Abstract
Transforming growth factor β (TGF-β) is a pluripotent cytokine that plays a pivotal role in regulating bone remodeling. In this study, we investigated the skeletal phenotype of 24-week-old transgenic female mice expressing a constitutively active TGF-β receptor type I (TβRI) under the control of inducible Mx1-Cre promoter. Poly(I:C) injection was used to induce expression of TβRI to generate Mx1;TβRI<sup>CA</sup> mice. In Mx1;TβRI<sup>CA</sup> mice, serum calcium levels were increased, while parathyroid hormone (PTH) levels were decreased. Micro-computed tomography (μCT) analysis revealed a significant increase in cancellous and cortical bone volume in femurs and mandibles of Mx1;TβRI<sup>CA</sup> mice compared to wild type mice. Histomorphometric analysis confirmed that this enhanced bone volume was associated with an increased number of osteoblasts and a reduced number of osteoclasts. Constitutive TβRI activation resulted in increased alkaline phosphatase and mineralization in primary cultures, while osteoclast cultures from Mx1;TβRI<sup>CA</sup> mice formed decreased TRAP positive osteoclasts compared to wild-type mice. Furthermore, qPCR analysis demonstrated upregulation of osteoblast differentiation markers, including Runx2, Sp7, Alpl, Col1a1, and Ptch2, while osteoclast-related genes such as Ctsk and Acp5 were downregulated in both femoral and mandibular bone in vivo. Similarly, osteoblast-related genes were increased in Mx1;TβRI<sup>CA</sup> osteoblasts, whereas osteoclast-related genes were decreased in Mx1;TβRI<sup>CA</sup> osteoclasts in vitro. Mx1;TβRI<sup>CA</sup> mice had increased microindentation. These results suggest that constitutive activation of TGF-β signaling promotes bone formation by stimulating osteoblast number while suppressing osteoclast number. This study highlights the important role of TGF-β in bone remodeling and homeostasis and may provide potential therapeutic targets for TβRI-associated bone diseases.