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Nephrectomy Induces Severe Bone Loss in Mice Expressing Constitutively Active TGFβ Receptor Type I
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DOI：10.3390/ijms26062704.png)
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Abstract
En 中文
Transforming growth factor beta (TGF-beta), 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-beta signaling on bone remodeling during CKD have not been investigated. Here, we determined the effects of TGF-beta receptor I (T beta RI) overexpression under the control of Mx1-Cre on bone remodeling in CKD mice (Mx1;T beta RICA-CKD mice). Our results demonstrated that kidney fibrosis and serum urea nitrogen levels were elevated in Mx1;T beta RICA-CKD mice compared to WT-CKD, indicating that T beta RI overexpression exacerbated renal injury during CKD. Serum calcium was decreased, while PTH was enhanced, in Mx1;T beta RICA-CKD mice. Mx1;T beta RICA-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;T beta RICA-CKD. Likewise, mRNA expression levels of an osteoclastogenesis marker, Tnfsf11/Tnfrsf11b, was increased, and osteoblast marker genes Runx2 and Sp7 were decreased in Mx1;T beta RICA-CKD mice. Mx1;T beta RICA-CKD mice displayed increased inflammatory cytokines levels. Together, our results indicated that in the setting of CKD, T beta RI 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.
Keywords:
TGF beta
osteoblast
osteoclast
bone
chronic kidney disease
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4.9
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44.5W
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