Analysis of osteoclast niche regulated by Wnt signals.

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We examined the role of Wnt signaling for the formation of osteoclast niche, and the results as follows. (1) The osteoclast niche was analyzed and characteristics of osteoclast precursors (quiescent osteoclast precursors, QOP) were clarified. (2) The role of noncanonical Wnt signaling in osteoclastogenesis was examined. Noncanonical Wnt signals (Wnt5a-Ror2 signals) were shown to play important roles in osteoclastogenesis. (3) Wnt5a-Ror2 signals enhanced RANKexpression in QOPs. Canonical Wnt signals did not appear to play a role in osteoclastogenesis. (4) GeneChip analysis was performed on QOPs to identify specific markers of QOPs. But we failed to isolate specific markers of QOPs. However, we found that osteoclasts specifically express Wnt5a.(5) IL-34 was identified as an important cytokine for generation of QOP in hematopoietic tissues. (6) Alveolar bone loss was examined in OPG-deficient (OPG?/?) mice and RANKL-overexpressing transgenic mice. OPG?/? mice were shown to be a use l model of periodontitis. (7) Administration of soluble form of Ror2 into collagen-induced arthritis mice effectively suppressed bone destruction.