Table 1.
Summary of osteoclast-secreted factors on bone remodeling.
| Factor secreted by osteoclasts | Effect on bone remodeling | Reference | |
|---|---|---|---|
| Osteoclast-derived enhancing factors of bone formation | |||
| Afamin | Afamin | Afamin secreted by osteoclasts in the early stage of differentiation stimulates preosteoblasts migration in vitro via the Akt-signaling pathway Afamin can prevent Wnt proteins from aggregating and deliver Wnt ligands to its receptors on the cell surface, which plays an important role in osteogenesis |
[56, 92] |
| BMP6 | Bone morphogenic protein 6 | Synthesis of BMPs has been confirmed in osteoclasts using immunocytochemistry and in situ hybridization BMP6 promotes osteoblast differentiation |
[93, 94] |
| C3a | Complement component 3a | C3 gene expression increases during osteoclastogenesis, and the cleavage product C3a is detected in the conditioned medium of osteoclasts C3a promotes osteoblast differentiation |
[95] |
| CT-1 | Cardiotrophin-1 | CT-1 promotes osteoblast differentiation Neonatal Ct-1−/− mice have decreased osteoblast numbers and BV/TV |
[96] |
| CTHCR1 | Collagen triple repeat containing1 | CTHCR1 is secreted by mature bone-resorbing osteoclasts CTHCR1 stimulates osteoblast differentiation Osteoclast-specific deletion of CTHCR1 in mice resulted in osteopenia due to reduced bone formation |
[97] |
| CXCL16 | Chemokine (C-X-C motif) ligand 16 | TGF-β1 released from the bone matrix during bone resorption induces CXCL16 production in osteoclasts, which promotes migration of osteoblast progenitors in bone remodeling | [98] |
| HGF | Hepatocyte growth factor | Osteoclasts can synthesize and secrete biologically active HGF, which promotes osteoblast proliferation and increases osteopontin expression in osteoblasts | [99, 100] |
| PDGF-BB | Platelet-derived growth factor BB | PDGF-BB induces MSC migration, but it inhibits osteoblast differentiation | [53, 101–103] |
| S1P | Sphingosine-1-phosphate | S1P stimulates MSC migration and promotes osteoblast differentiation Raising S1P levels in adult mice markedly increased bone formation |
[104–106] |
| SLIT3 | slit guidance ligand 3 | Osteoclast-secreted SLIT3 synchronously inhibits bone resorption and stimulates bone formation SLIT3 injection in mice markedly rescued bone loss after ovariectomy surgery |
[107] |
| TRAP | Tartrate-resistant acid phosphatase | TRAP promotes osteoblast differentiation TRAP overexpressing transgenic mice have an increased rate of bone turnover |
[108, 109] |
| Vesicular RANK | Vesicular TNF receptor superfamily member 11A | Mature OCs secrete vesicular RANK, which binds osteoblastic RANKL and promotes bone formation via triggering RANKL reverse signaling | [110] |
| Wnt10b | Wnt family member 10b | Wnt10b expression increases during osteoclastogenesis Wnt10b promotes mineralization |
[104] |
|
| |||
| Osteoclast-derived inhibiting factors of bone formation | |||
| LIF | Leukemia inhibitor factor | LIF inhibits TGFb1-induced osteoblast migration | [98] |
| Sema4D | Semaphorin 4D | Sema4D suppresses bone formation by inhibiting IGF-1 signaling Sema4d-/- mice show an osteosclerotic phenotype due to augmented bone formation |
[111] |
| SOST | Sclerostin | SOST is expressed in osteoclasts from aged mice and inhibits osteoclast-mediated stimulation of mineralization | [112] |
| Exosomal miR-214-3p | Exosomal miR-214-3p | miR-214-3p reduces bone formation in elderly women with fractures and in ovariectomized mice | [113, 114] |