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• W2306616852 startingPage "E811" @default.
• W2306616852 abstract "Osteoblastic cells indirectly induce osteoclastogenesis in the bone microenvironment by expressing paracrine factors such as RANKL and M-CSF, leading to increased bone resorption. These cytokines can be regulated by a variety of intracellular pathways, which include G protein-coupled receptor signaling. To explore how enhanced signaling of the Gα q/11 pathway in osteoblast lineage cells may mediate osteoclast formation, we cocultured wild-type (WT) preosteoclasts with BMSCs derived from either WT or transgenic mice with osteoblast-specific overexpression of Gα 11 (G 11 -Tg). G 11 -Tg cocultures had elevated osteoclast numbers with greater resorptive capacity and increased expression of Rankl, Rankl:Opg (osteoprotegerin), and M-csf compared with cocultures with WT BMSCs. As well, cocultures with G 11 -Tg BMSCs required a higher concentration of OPG to inhibit osteoclast formation and less angiotensin II to increase osteoclast size. These indicate that G 11 -Tg osteoblasts drive the increased osteoclast formation and osteopenia seen in G 11 -Tg mice. Pamidronate treatment of G 11 -Tg mice restored the trabecular bone loss phenotype, as bone mineral density, bone volume, trabecular number, separation, and expressions of osteoblastic and osteoclastic genes were comparable with WT parameters. These changes were characterized by enhanced accumulation of calcified cartilage in trabecular bone, demonstrating that resorption of the cartilaginous intermediate by osteoclasts is more affected by bisphosphonate treatment in G 11 -Tg mice. In conclusion, overexpression of Gα 11 in osteoblastic cells promotes osteoclastogenesis by upregulation of Rankl and M-csf and bone loss by increased osteoclast resorption of the trabecular bone and cartilaginous matrix." @default.
• W2306616852 created "2016-06-24" @default.
• W2306616852 creator A5015255127 @default.
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• W2306616852 creator A5091430658 @default.
• W2306616852 date "2016-05-15" @default.
• W2306616852 modified "2023-10-17" @default.
• W2306616852 title "Elevated Gα11 expression in osteoblast lineage cells promotes osteoclastogenesis and leads to enhanced trabecular bone accrual in response to pamidronate" @default.
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• W2306616852 doi "https://doi.org/10.1152/ajpendo.00049.2016" @default.
• W2306616852 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27006198" @default.
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