Hyperthyroidism-driven bone loss depends on BMP receptor Bmpr1a expression in osteoblasts.

Abstract

Hyperthyroidism is a well-known trigger of high bone turnover that can lead to the development of secondary osteoporosis. Previously, we have shown that blocking bone morphogenetic protein (BMP) signaling systemically with BMPR1A-Fc can prevent bone loss in hyperthyroid mice. To distinguish between bone cell type-specific effects, conditional knockout mice lacking Bmpr1a in either osteoclast precursors (LysM-Cre) or osteoprogenitors (Osx-Cre) were rendered hyperthyroid and their bone microarchitecture, strength and turnover were analyzed. While hyperthyroidism in osteoclast precursor-specific Bmpr1a knockout mice accelerated bone resorption leading to bone loss just as in wildtype mice, osteoprogenitor-specific Bmpr1a deletion prevented an increase of bone resorption and thus osteoporosis with hyperthyroidism. In vitro, wildtype but not Bmpr1a-deficient osteoblasts responded to thyroid hormone (TH) treatment with increased differentiation and activity. Furthermore, we found an elevated Rankl/Opg ratio with TH excess in osteoblasts and bone tissue from wildtype mice, but not in Bmpr1a knockouts. In line, expression of osteoclast marker genes increased when osteoclasts were treated with supernatants from TH-stimulated wildtype osteoblasts, in contrast to Bmpr1a-deficient cells. In conclusion, we identified the osteoblastic BMP receptor BMPR1A as a main driver of osteoporosis in hyperthyroid mice promoting TH-induced osteoblast activity and potentially its coupling to high osteoclastic resorption.

• Authors: Franziska Lademann, Eddy Rijntjes, Josef Köhrle, Elena Tsourdi, Lorenz C Hofbauer, Martina Rauner
• Journal: Communications biology (Commun Biol) Vol. 7 Issue 1 Pg. 548 (May 08 2024) ISSN: 2399-3642 [Electronic] England
• PMID: 38719881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2024. The Author(s).

Chemical References

• Bone Morphogenetic Protein Receptors, Type I
• Bmpr1a protein, mouse

Topics

• Animals
• Bone Morphogenetic Protein Receptors, Type I (genetics, metabolism)
• Osteoblasts (metabolism)
• Hyperthyroidism (metabolism, genetics, complications)
• Mice
• Mice, Knockout
• Bone Resorption (metabolism, genetics)
• Osteoporosis (metabolism, genetics, etiology, pathology)
• Osteoclasts (metabolism)
• Male
• Cell Differentiation