Impaired bone formation and increased osteoclastogenesis in mice lacking chemokine (C‐C motif) ligand 5 (Ccl5)

摘要: Chemokines play crucial roles in the recruitment of specific hematopoietic cell types, and some them have been suggested to be involved regulation bone remodeling. Because we previously observed that chemokine (C-C motif) ligand 2 (Ccl2) Ccl5 are direct target genes noncanonical Wnt signaling osteoblasts, analyzed skeletal phenotypes Ccl2-deficient Ccl5-deficient mice. In line with previous studies, mice display a moderate reduction osteoclastogenesis at age 6 months. contrast, 6-month-old osteopenia associated decreased formation increased osteoclastogenesis. Moreover, unlike wild-type mice, large areas their trabecular endocortical surfaces not covered by osteoblasts or bone-lining cells, this is severe endosteal formation. Although phenotype diminishes age, it important could further identify reduced number osteal macrophages because type has reported promote also osteoclastogenesis, finally addressed question whether differentiate into osteoclasts and/or secrete inhibitors For purpose isolated these cells CD11b affinity purification from calvarial cultures characterized ex vivo. Here found they unable osteoclasts, but conditioned medium mediates an antiosteoclastogenic effect, possibly caused interleukin-18 (IL-18), inhibitor expressed macrophages. Taken together, our data provide vivo evidence supporting role best knowledge, represent first model spontaneous partial deficiency macrophages, recently identified type, whose impact on remodeling just beginning understood.