Nephrectomy Induces Severe Bone Loss in Mice Expressing Constitutively Active TGFβ Receptor Type I
1
Issued Date
2025-03-17
Resource Type
eISSN
14220067
Scopus ID
2-s2.0-105002283985
Pubmed ID
40141345
Journal Title
International journal of molecular sciences
Volume
26
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
International journal of molecular sciences Vol.26 No.6 (2025)
Suggested Citation
Toejing P., Myint O., Leelahavanichkul A., Sridurongrit S., Greenblatt M.B., Lotinun S. Nephrectomy Induces Severe Bone Loss in Mice Expressing Constitutively Active TGFβ Receptor Type I. International journal of molecular sciences Vol.26 No.6 (2025). doi:10.3390/ijms26062704 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109624
Title
Nephrectomy Induces Severe Bone Loss in Mice Expressing Constitutively Active TGFβ Receptor Type I
Corresponding Author(s)
Other Contributor(s)
Abstract
Transforming growth factor beta (TGF-β), a master regulator of renal fibrosis, is the hallmark of chronic kidney disease (CKD) progression, and CKD worsens bone remodeling. However, the effects of the dysregulation of TGF-β signaling on bone remodeling during CKD have not been investigated. Here, we determined the effects of TGF-β receptor I (TβRI) overexpression under the control of Mx1-Cre on bone remodeling in CKD mice (Mx1;TβRICA-CKD mice). Our results demonstrated that kidney fibrosis and serum urea nitrogen levels were elevated in Mx1;TβRICA-CKD mice compared to WT-CKD, indicating that TβRI overexpression exacerbated renal injury during CKD. Serum calcium was decreased, while PTH was enhanced, in Mx1;TβRICA-CKD mice. Mx1;TβRICA-CKD mice displayed severe osteopenia as assessed by uCT in both femurs and mandibles. An histomorphometric analysis showed that tibial cancellous bone volume was decreased in Mx1;TβRICA-CKD. Likewise, mRNA expression levels of an osteoclastogenesis marker, Tnfsf11/Tnfrsf11b, was increased, and osteoblast marker genes Runx2 and Sp7 were decreased in Mx1;TβRICA-CKD mice. Mx1;TβRICA-CKD mice displayed increased inflammatory cytokines levels. Together, our results indicated that in the setting of CKD, TβRI overexpression induced both CKD progression and the dysregulation of bone remodeling, leading to severe bone loss. As such, these data provide an avenue for the future development of therapeutics for CKD-induced osteoporosis.