First Author | Deng R | Year | 2022 |
Journal | Adv Sci (Weinh) | Volume | 9 |
Issue | 3 | Pages | e2103343 |
PubMed ID | 34854257 | Mgi Jnum | J:331616 |
Mgi Id | MGI:7378602 | Doi | 10.1002/advs.202103343 |
Citation | Deng R, et al. (2022) Periosteal CD68(+) F4/80(+) Macrophages Are Mechanosensitive for Cortical Bone Formation by Secretion and Activation of TGF-beta1. Adv Sci (Weinh) 9(3):e2103343 |
abstractText | 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 beta (TGF-beta), 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-beta1 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-beta1 secretion. Importantly, CD68(+) F4/80(+) macrophages activate TGF-beta1 by expression and secretion of thrombospondin-1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading-induced TGF-beta 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-beta1 for periosteal bone formation. |