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Activated type I receptors initiate intracellular signaling via phosphorylation of the specific Smad protein R-Smads ( 3.2.2 Role of MOTS-c in osteoblasts mediated via the TGF-/Smad pathway Two factors, TGF- and Smad, act synergistically to participate in the regulation of osteoblasts, directly or indirectly promoting osteoblast differentiation, inhibiting bone resorption, and promoting bone formation

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Treatment with semaglutide reduced pre-stroke IGF-1 levels compared with HFD-fed vehicle (PBS)-treated mice, but levels remained higher than in mice fed a standard diet (Fig