Osteocyte survival is key to bone homeostasis and is perturbed in menopause and aging. However, it remains unknown how osteocyte-mediated maintenance of the skeleton is regulated by the osteoprotective factor semaphorin 3A (Sema3A), a secreted protein that is known to reduce bone resorption and enhance bone formation. Here, we show that estrogen induces osteocyte expression of Sema3A, which acts on its receptor on osteocytes to promote their survival and maintain bone homeostasis. Postnatal global and conditional deletion of Sema3a in osteoblastic cells resulted in a severe osteoporotic phenotype marked by fewer osteocytes. This phenotype was recapitulated by osteocyte-specific deficiency of either Sema3A or its receptor component neuropilin-1 (Nrp1). A stimulator of soluble guanylate cyclase-cGMP signaling mimicked Sema3A action and ameliorated bone loss after ovariectomy. We further show that serum levels of SEMA3A decreased with age or after menopause in humans. Thus, we provide a mechanistic insight into the estrogen action and a promising therapeutic approach to protect against bone-related aging.
Pubmed ID: 30661929 RIS Download
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
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View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-VASP (Ser239)
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View all literature mentionsCell line IDG-SW3 is a Conditionally immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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