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- Title
Soluble RANKL contributes to osteoclast formation in adult mice but not ovariectomy-induced bone loss.
- Authors
Xiong, Jinhu; Cawley, Keisha; Piemontese, Marilina; Fujiwara, Yuko; Zhao, Haibo; Goellner, Joseph J.; O’Brien, Charles A.
- Abstract
Receptor activator of NFkB ligand (RANKL) is a TNF-family cytokine required for osteoclast formation, as well as immune cell and mammary gland development. It is produced as a membrane-bound protein that can be shed to form a soluble protein. We created mice harboring a sheddase-resistant form of RANKL, in which soluble RANKL is undetectable in the circulation. Lack of soluble RANKL does not affect bone mass or structure in growing mice but reduces osteoclast number and increases cancellous bone mass in adult mice. Nonetheless, the bone loss caused by estrogen deficiency is unaffected by the lack of soluble RANKL. Lymphocyte number, lymph node development, and mammary gland development are also unaffected by the absence of soluble RANKL. These results demonstrate that the membrane-bound form of RANKL is sufficient for most functions of this protein but that the soluble form does contribute to physiological bone remodeling in adult mice. RANKL is a cytokine produced as a membrane-bound and a secreted protein. Here, using mice lacking soluble RANKL, the authors show that the secreted protein is important for osteoclast function, but not for mammary gland and lymphocyte development.
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-05244-y