Bone Morphogenetic Protein 2 Stimulates Osteoclast Differentiation and Survival Supported by Receptor Activator of Nuclear Factor-κB Ligand
Bone is a major storage site for TGFβ superfamily members, including TGFβ and bone morphogenetic proteins. It is believed that these cytokines are released from bone during bone resorption. Recent studies have shown that both RANKL and macrophage colony-stimulating factor are two essential factors p...
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Published in | Endocrinology (Philadelphia) Vol. 142; no. 8; pp. 3656 - 3662 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.08.2001
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Online Access | Get full text |
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Summary: | Bone is a major storage site for TGFβ superfamily members,
including TGFβ and bone morphogenetic proteins. It is believed that
these cytokines are released from bone during bone resorption. Recent
studies have shown that both RANKL and macrophage colony-stimulating
factor are two essential factors produced by osteoblasts for inducing
osteoclast differentiation. In the present study we examined the
effects of bone morphogenetic protein-2 on osteoclast differentiation
and survival supported by RANKL and/or macrophage colony-stimulating
factor. Mouse bone marrow-derived macrophages differentiated into
osteoclasts in the presence of RANKL and macrophage colony-stimulating
factor. TGFβ superfamily members such as bone morphogenetic
protein-2, TGFβ, and activin A markedly enhanced osteoclast
differentiation induced by RANKL and macrophage colony-stimulating
factor, although each cytokine alone failed to induce osteoclast
differentiation in the absence of RANKL. Addition of a soluble form of
bone morphogenetic protein receptor type IA to the culture markedly
inhibited not only osteoclast formation induced by RANKL and bone
morphogenetic protein-2, but also the basal osteoclast formation
supported by RANKL alone. Either RANKL or macrophage colony-stimulating
factor stimulated the survival of purified osteoclasts. Bone
morphogenetic protein-2 enhanced the survival of purified osteoclasts
supported by RANKL, but not by macrophage colony-stimulating factor.
Both bone marrow macrophages and mature osteoclasts expressed bone
morphogenetic protein-2 and bone morphogenetic protein receptor type IA
mRNAs. An EMSA revealed that RANKL activated nuclear factor-κB in
purified osteoclasts. Bone morphogenetic protein-2 alone did not
activate nuclear factor-κB, but rather inhibited the activation of
nuclear factor-κB induced by RANKL in purified osteoclasts. These
findings suggest that bone morphogenetic protein-mediated signals
cross-communicate with RANKL-mediated ones in inducing osteoclast
differentiation and survival. The enhancement of RANKL-induced survival
of osteoclasts by bone morphogenetic protein-2 appears unrelated to
nuclear factor-κB activation. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.142.8.8300 |