Resumo

MARTIN-MILLAN, M et al. The Wnt/β-catenin pathway decreases the amount of osteoclasts in the bone and promotes its apoptosis. Rev Osteoporos Metab Miner [online]. 2019, vol.11, n.2, pp.39-45.  Epub 20-Jan-2020. ISSN 2173-2345.  https://dx.doi.org/10.4321/s1889-836x2019000200002.

The activation of Wnt/βcatenin signaling in cells of the osteoblastic lineage leads to an increase in bone mass through a dual mechanism: increasing osteoblastogenesis and decreasing osteoclastogenesis. The predominance of one mechanism over another depends on the maturational state of the osteoblast in which βcatenin accumulation occurs. The activation of Wnt/βcatenin signaling in cells of the osteoclastic lineage and its possible effects on the regulation of bone mass is less known. Previous studies have shown that conditional ablation of βcatenin in osteoclasts induces a decrease in bone mass associated with an increase in osteoclasts, and this fact has been attributed to an increase in osteoclastogenesis. However, other alternative possibilities have not been evaluated, such as that a decrease in the normal osteoclast apoptosis may also contribute to the greater number of osteoclasts. In this paper, to obtain information about this fact, we generated mice in which βcatenin was selectively eliminated from cells of the monocyte/macrophage lineage using an allele flanked by βcatenin (Catnb.) together with the deletion line LisozimaMCre (LysMCre). The threeβdimensional analysis of the bones of the Catnbf/f;LysM mice revealed a significant decrease in the thickness of the femoral cortex, while the trabecular bone of the vertebrae was not affected. This phenotype was associated with a greater number of osteoclasts on the bone surface. The number of osteoclasts in the cultures from the Catnbf/f;LysM mice was twice as high as in the cultures obtained from the control mice. The administration of WNT3a attenuated the osteoclast formation induced by MβCSF and RANKL in vitro. In addition, WNT3a promoted apoptosis of osteoclasts, and this effect was counteracted, both by the presence of DKK1 and by the absence of βcatenin. Taken together, these results support a cellular autonomous effect of βcatenin in the osteoclast, and provide convincing evidence of the proapoptotic role of βcatenin in these cells.

Palavras-chave : bone; osteoclasts; lysozyme M, β-catenin; Wnt; WNT3a.

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