Abstract
Osteoporosis (OP) is a major skeletal disorder for the old man. The fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by osteoblasts and osteocytes. However, the regulatory mechanisms of FGF23 in the progression of osteoporosis remain poorly understood. This study aims to explore the downstream regulating pathway of FGF23 in postmenopausal osteoporosis. The rat model of osteoporosis was established through ovariectomy (OVX). The investigation demonstrated that the serum levels of FGF23 and the phosphorylation levels of JAK2, STAT1, and STAT3 were up-regulated in the OVX + NVP-BGJ398 group while were down-regulated in the OVX + Anti-FGF23 group than that in the OVX group. Moreover, the JAK2/STAT1/3 inhibitor, AG490 promoted the OVX-induced increase in the osteocalcin, ALP, BALP, TRAP, and CTX-I levels. Besides, AG490 enhanced cartilage lesions and increased TUNEL-positive chondrocytes in the OVX group. In addition, higher protein expression of MMP-1 and MMP-13 and lower expression of COX-II were observed in the OVX + AG490 group than that in the OVX group. Our findings suggested that FGF23 was involved in the progression of osteoporosis via the JAK/STAT signaling pathway.
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