Periosteal CD68⁺F4/80⁺ Macrophages Are Mechanosensitive for Cortical Bone Formation by Secretion and Activation of TGF‐β1

Abstract

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.

Bovine Serum Albumin-Coated Ceria Nanoparticles Activate the TGF-β Signaling Pathway for Periodontal Bone Regeneration

“…The results showed that five genes were significantly up-regulated in the CeO 2 @BSA group (Figure E), which was consistent with the sequencing results. TGF-β1 belongs to the TGF-β subfamily, which regulates cell growth and differentiation . The expression level of TGF-β1 protein was increased after CeO 2 @BSA treatment, which indicated that the TGF-β signaling pathway was indeed activated (Figure E).…”

“…TGF-β1 belongs to the TGF-β subfamily, which regulates cell growth and differentiation. 62 The expression level of TGF-β1 protein was increased after CeO 2 @BSA treatment, which indicated that the TGF-β signaling pathway was indeed activated (Figure 3E). Thus, the TGF-β signaling pathway may mediate CeO 2 @BSA-induced bone differentiation of hPDLCs.…”

Smart, Biomimetic Periosteum Created from the Cerium(III, IV) Oxide-Mineralized Eggshell Membrane

“…Macrophages were isolated from the bone marrow of mice according to a previously described method and were cultured in CCM. 42,43 Mouse macrophage colony-stimulating factor (M-CSF; 20 ng/mL; Peprotech Inc., Rocky Hill, NJ, USA) was added to the CCM for 6 days prior to the experiment. SC cells were isolated from the sciatic nerve segments of neonatal Sprague−Dawley (SD) rats and cultured in CCM with no more than two passages prior to use.…”

Unraveling the Mechanobiology Underlying Traumatic Brain Injury with Advanced Technologies and Biomaterials

“…[92] Furthermore, in an mTBI model, repetitive mechanical impact has been shown to induce reactive astrogliosis and glial scar formation. [93] While it is believed that mechanical cues coregulate the phenotype and phagocytosis of macrophages, [94][95][96] how these cues affect microglia functions under the altered brain mechanical microenvironment after TBI needs to be further elucidated. Those microglia and astrocyte mechanobiology will be conducive to our understanding of the chronic consequences of TBI from a braininflammation perspective.…”