[Progress of parathyroid hormone regulating bone metabolism via different signaling pathways]

Parathyroid hormone is one kind of osteoanabolic agents widely used in clinic for osteoporosis. However, parathyroid hormone needs to be further optimized in the treatment of osteoporosis due to its two way regulatory effect of bone formation with low-dose intermittent treatmentand bone resorption with high-dosecontinuous treatment. Hence, based on the molecular mechanism of parathyroid hormone regulating bone metabolism, we conclude that parathyroid hormone regulates bone metabolism mainly through the following signaling pathways: (1) Gs/cAMP/PKA signaling pathway, whichis the main mechanism of parathyroid hormone regulating bone metabolism to lead to bone formation or bone resorption. (2) G_q/11/PLC/PKC signaling pathway, whose f_6_main function is to inhibit osteogenesis.(3)nonPLC/PKC signaling pathway, which is considered to playosteogenic effect, but whose specific content is not completely clear. (4) β-arrestin signaling pathway, which can only induceosteogenesis without osteoclastic activation byreceptor desensitization and endocytosis. In this work, we will review the specific contents and functions of the four main signaling pathways activated by parathyroid hormoneto find more optimalosteoanabolic agents. Among them, SOST and Dickkopf-1 monoclonal antibodies are novel targeted drugs. Parathyroid hormone-related peptide that specifically activates the nonPLC/PKC signaling pathway or β-arrestin signaling pathway is worthy of further development and application.