TY - JOUR
T1 - Periosteal CD68+F4/80+ Macrophages Are Mechanosensitive for Cortical Bone Formation by Secretion and Activation of TGF-β1
AU - Deng, Ruoxian
AU - Li, Changwei
AU - Wang, Xiao
AU - Chang, Leilei
AU - Ni, Shuangfei
AU - Zhang, Weixin
AU - Xue, Peng
AU - Pan, Dayu
AU - Wan, Mei
AU - Deng, Lianfu
AU - Cao, Xu
N1 - Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH
PY - 2022/1/25
Y1 - 2022/1/25
N2 - Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism is poorly understood. Here, it is shown that myeloid-lineage cells differentiate into subgroups and regulate periosteal bone formation in response to mechanical loading. Mechanical loading on tibiae significantly increases the number of periosteal myeloid-lineage cells and the levels of active transforming growth factor β (TGF-β), resulting in cortical bone formation. Knockout of Tgfb1 in myeloid-lineage cells attenuates mechanical loading-induced periosteal bone formation in mice. Moreover, CD68+F4/80+ macrophages, a subtype of myeloid-lineage cells, express and activate TGF-β1 for recruitment of osteoprogenitors. Particularly, mechanical loading induces the differentiation of periosteal CD68+F4/80− myeloid-lineage cells to the CD68+F4/80+ macrophages via signaling of piezo-type mechanosensitive ion channel component 1 (Piezo1) for TGF-β1 secretion. Importantly, CD68+F4/80+ macrophages activate TGF-β1 by expression and secretion of thrombospondin-1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading-induced TGF-β activation and recruitment of osteoprogenitors in the periosteum. The results suggest that periosteal myeloid-lineage cells respond to mechanical forces and consequently produce and activate TGF-β1 for periosteal bone formation.
AB - Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism is poorly understood. Here, it is shown that myeloid-lineage cells differentiate into subgroups and regulate periosteal bone formation in response to mechanical loading. Mechanical loading on tibiae significantly increases the number of periosteal myeloid-lineage cells and the levels of active transforming growth factor β (TGF-β), resulting in cortical bone formation. Knockout of Tgfb1 in myeloid-lineage cells attenuates mechanical loading-induced periosteal bone formation in mice. Moreover, CD68+F4/80+ macrophages, a subtype of myeloid-lineage cells, express and activate TGF-β1 for recruitment of osteoprogenitors. Particularly, mechanical loading induces the differentiation of periosteal CD68+F4/80− myeloid-lineage cells to the CD68+F4/80+ macrophages via signaling of piezo-type mechanosensitive ion channel component 1 (Piezo1) for TGF-β1 secretion. Importantly, CD68+F4/80+ macrophages activate TGF-β1 by expression and secretion of thrombospondin-1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading-induced TGF-β activation and recruitment of osteoprogenitors in the periosteum. The results suggest that periosteal myeloid-lineage cells respond to mechanical forces and consequently produce and activate TGF-β1 for periosteal bone formation.
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U2 - 10.1002/advs.202103343
DO - 10.1002/advs.202103343
M3 - Article
C2 - 34854257
AN - SCOPUS:85120381299
SN - 2198-3844
VL - 9
JO - Advanced Science
JF - Advanced Science
IS - 3
M1 - 2103343
ER -