CaMKII inhibition due to TRIC-B loss-of-function dysregulates SMAD signaling in osteogenesis imperfecta

•Lack of TRIC-B in osteoblasts strongly impairs skeleton growth and structure, leading to bone fractures.•In absence of TRIC-B, the impaired Ca2+ flux from endoplasmic reticulum to cytosol is associated to delayed osteoblast differentiation and decreased collagen synthesis that cause reduced collagen incorporation in the extracellular matrix and poor mineralization.•An impaired SMAD signaling in mutant mice and in OI patient osteoblasts explains the osteoblast malfunction.•The reduced SMAD phosphorylation and nuclear translocation are mainly caused by alteration in Ca2+ calmodulin kinase II (CaMKII)-mediated signaling.