Estrogen-dependent and C-C chemokine receptor-2–dependent pathways determine osteoclast behavior in osteoporosis

摘要: Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that C-C chemokine receptor-2 (CCR2) crucially involved in balancing mass. CCR2-knockout mice have high mass owing a decrease number, size and function osteoclasts. In normal mice, activation CCR2 osteoclast progenitor cells results both nuclear factor-kappaB (NF-kappaB) extracellular signal-related kinase 1 2 (ERK1/2) signaling but not p38 mitogen-activated protein or c-Jun N-terminal kinase. The induction NF-kappaB ERK1/2 turn leads increased surface expression receptor activator (RANK, encoded by Tnfrsf11a), making more susceptible RANK ligand-induced osteoclastogenesis. ovariectomized model postmenopausal osteoporosis, upregulated on wild-type preosteoclasts, thus increasing these their osteoclastogenic potential, whereas are resistant ovariectomy-induced loss. These data reveal previously undescribed pathway which RANK, osteoclasts homeostasis regulated health disease.