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Journal Article
SOXC are critical regulators of adult bone mass
2024
Overview
Pivotal in many ways for human health, the control of adult bone mass is governed by complex, incompletely understood crosstalk namely between mesenchymal stem cells, osteoblasts and osteoclasts. The SOX4, SOX11 and SOX12 (SOXC) transcription factors were previously shown to control many developmental processes, including skeletogenesis, and
SOX4
was linked to osteoporosis, but how SOXC control adult bone mass remains unknown. Using SOXC loss- and gain-of-function mouse models, we show here that SOXC redundantly promote prepubertal cortical bone mass strengthening whereas only SOX4 mitigates adult trabecular bone mass accrual in early adulthood and subsequent maintenance. SOX4 favors bone resorption over formation by lowering osteoblastogenesis and increasing osteoclastogenesis. Single-cell transcriptomics reveals its prevalent expression in
Lepr
+
mesenchymal cells and ability to upregulate genes for prominent anti-osteoblastogenic and pro-osteoclastogenic factors, including interferon signaling-related chemokines, contributing to these adult stem cells’ secretome. SOXC, with SOX4 predominantly, are thus key regulators of adult bone mass.
Angelozzi
et al
. uncover key mechanisms involved in physiological and pathological bone mass remodeling by showing that SOXC transcription factors regulate the bone formation and resorption balance via critical roles in LepR
+
mesenchymal stem cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/89
/ 14
/ 14/19
/ 38/39
/ 38/88
/ 38/91
/ 45/100
/ 45/90
/ 64/60
/ Adult
/ Animals
/ Humanities and Social Sciences
/ Humans
/ Mesenchymal Stem Cells - metabolism
/ Mice
/ Science
/ SOXC Transcription Factors - genetics
