BMP3b regulates bone mass by inhibiting BMP signaling.

Autor: Kodama N; Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan; Division of Oral Medicine, Kyushu Dental University, Kokurakita, Kitakyushu, Fukuoka, Japan., Matsubara T; Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan., Yoshimura A; Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan., Nagano K; Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan., Hino J; Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Japan., Tsuji K; Department of Orthopedic Surgery, Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan., Ikedo A; Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan., Imai Y; Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan., Yaginuma T; Division of Oral and Maxillofacial Surgery, Kyushu Dental University, Kokurakita, Kitakyushu, Fukuoka, Japan., Yuan Q; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China., Morikawa K; Division of Developmental Stomatognathic Function Science, Kyushu Dental University, Kokurakita, Kitakyushu, Fukuoka, Japan., Ono Y; Department of Muscle Development and Regeneration, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan; Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo, Japan., Shirakawa T; Division of Orofacial Functions and Orthodontics, Kyushu Dental University, Kokurakita, Kitakyushu, Fukuoka, Japan., Addison WN; Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan., Yoshioka I; Division of Oral Medicine, Kyushu Dental University, Kokurakita, Kitakyushu, Fukuoka, Japan., Kokabu S; Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan. Electronic address: r14kokabu@fa.kyu-dent.ac.jp.
Jazyk: angličtina
Zdroj: Bone [Bone] 2025 Jan; Vol. 190, pp. 117303. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.bone.2024.117303
Abstrakt: Bone morphogenetic protein 3b (BMP3b), also known as growth differentiation factor 10 (GDF10), is a non-osteogenic BMP highly expressed in the skeleton. Although in vitro studies have shown that BMP3b suppresses osteoblast differentiation, the physiological role of BMP3b in regulating bone mass in vivo remains unknown. Here, we show that BMP3b deletion in mice leads to a high bone mass phenotype via an unexpected novel mechanism involving de-repression of canonical BMP/Smad signaling. BMP3b null mice were viable, and exhibited no significant difference in body size compared to wildtype control. Trabecular bone parameters assessed by histomorphometry and μCT, revealed a significant increase in bone volume and bone mineral density. Expression of osteoblast-differentiation genes were elevated in bone tissue of BMP3b null mice, whereas expression of osteoclast-related genes remained unchanged. Consistent with this, Bmp3b was highly expressed in osteoblasts relative to osteoclast cells. Ex-vivo culture of primary bone marrow mesenchymal stem cells (BMSCs) and primary bone marrow-derived osteoclasts revealed that inactivation of BMP3b enhances osteogenesis without affecting osteoclastogenesis. Mechanistically, we found that BMP3b suppressed BMP4-induced Smad1/5 phosphorylation and inhibited the activity of a BMP4-driven Id-1 luciferase reporter. Protein-protein interaction assays revealed that BMP3b competitively interfered with the association of BMP4 and BMP type I receptors. These findings suggest that BMP3b regulates bone mass by acting as a BMP receptor antagonist. Thus, maintenance of bone mass involves antagonism of canonical BMP/Smad signaling by a member of the BMP family.
Competing Interests: Declaration of competing interest The authors declare that this article and related all data are original, is not under consideration by any other journals. The authors also declare that we will not submit this manuscript to any other journals during the review period of Bone. The authors also confirm that data from previously published papers have not been used in this manuscript and agree to provide information about any relevant publications.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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