SMAD1/5 signaling in osteoclasts regulates bone formation via coupling factors

• DOI: 10.1371/journal.pone.0203404
• Publication Date: 2018-09-06T17:48:21Z
• Authors: Amy Tasca; Kristina Astleford; Nicholas C. Blixt; Eric D. Jensen; Rajaram Gopalakri...; Kim C. Mansky
• Keywords: Bone remodeling

Bone remodeling occurs via coupling between bone resorption by osteoclasts and formation osteoblasts. The mechanisms that regulate osteoclast signals to osteoblasts are not well understood. Published studies have reported BMP signaling in targets. To investigate the necessity of canonical on differentiation coupling, we mated Smad1fl/fl; Smad5fl/fl mice c-Fms-Cre mice. We analyzed male at 3 months age determine skeletal phenotype Smad5fl/fl;c-Fms-Cre (SMAD1/5 cKO) There was a 1.2-fold decrease trabecular BV/TV SMAD1/5 cKO. Analyses serum markers cKO mice, showed significant increase CTX-1 (1.5 fold) TRAP ELISA (3 compared control In these same there 1.3-fold cortical thickness. Consistent with thickness, found 3-fold osteoblast activity as measured P1NIP assay from explain changes thickness P1NP activity, determined conditioned media cultures enhanced mineralization an cell line factors expressed Wnt1 (4.5-fold increase), Gja1 (3-fold increase) Sphk1 (1.5-fold were all upregulated osteoclasts. Lastly treated dorsomorphin, chemical inhibitor signaling, demonstrates expression similar Previous demonstrated TGF-β leads increases WNT1 Therefore, our data suggest pathways could act antagonistic fashion through other factors.