Pip5k1c expression in osteocytes regulates bone remodeling in mice

• Published in: Journal of orthopaedic translation 2024-03, Vol.45, p.36-47
• Main Authors: Lin, Sixiong, Tao, Chu, Yan, Qinnan, Gao, Huanqing, Qin, Lei, Zhong, Yiming, Yao, Qing, Zhang, Peijun, Yang, Jiaming, Zou, Xuenong, Xiao, Guozhi
• Format: Article
• Language: English
• Subjects: Bone mass; Osteocyte; Pip5k1c; Sclerostin
• ISSN: 2214-031X
• DOI: 10.1016/j.jot.2023.10.008

The role of osteocytes in maintaining bone mass has been progressively emphasized. Pip5k1c is the most critical isoform among PIP5KIs, which can regulate cytoskeleton, biomembrane, and Ca2+ release of cells and participate in many processes, such as cell adhesion, differentiation, and apoptosis. However, its expression and function in osteocytes are still unclear. To determine the function of Pip5k1c in osteocytes, the expression of Pip5k1c in osteocytes was deleted by breeding the 10-kb mouse Dmp1-Cre transgenic mice with the Pip5k1cfl/fl mice. Bone histomorphometry, micro-computerized tomography analysis, immunofluorescence staining and western blotting were used to determine the effects of Pip5k1c loss on bone mass. In vitro, we explored the mechanism by siRNA knockdown of Pip5k1c in MLO-Y4 cells. Pip5k1c expression was decreased in osteocytes in senescent and osteoporotic tissues both in humans and mice. Loss of Pip5k1c in osteocytes led to a low bone mass in long bones and spines and impaired biomechanical properties in femur, without changes in calvariae. The loss of Pip5k1c resulted in the reduction of the protein level of type 1 collagen in tibiae and MLO-Y4 cells. Osteocyte Pip5k1c loss reduced the osteoblast and bone formation rate with high expression of sclerostin, impacting the osteoclast activities at the same time. Moreover, Pip5k1c loss in osteocytes reduced expression of focal adhesion proteins and promoted apoptosis. Our studies demonstrate the critical role and mechanism of Pip5k1c in osteocytes in regulating bone remodeling. Osteocyte has been considered to a key role in regulating bone homeostasis. The present study has demonstrated that the significance of Pip5k1c in bone homeostasis by regulating the expression of collagen, sclerostin and focal adhesion expression, which provided a possible therapeutic target against human metabolic bone disease. [Display omitted]