Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA-211-5p and repressing Janus kinase 2/Signal transducer and activator of transcription 3 pathway.

Abstract

This study explored the effect of Eupatilin on postmenopausal osteoporosis and explored the mechanisms associated with miR-211-5p. First, the rats were given intragastric administration of Eupatilin every day and subcutaneously injected once a week with oligonucleotides or plasmids that interfered with the expression of miR-211-5p or Janus kinase 2 (JAK2). After 4weeks, a rat model of osteoporosis was established. Then, serum alkaline phosphatase, calcium and phosphorus levels were detected, as well as femur bone mineral density and biomechanical parameters. HE staining and Masson staining were applied for detecting the pathological condition of femur while immunohistochemical staining was for detecting the positive expression of osteocalcin. In addition, MC3T3-E1 cells were transfected with plasmid vectors interfering with miR-211-5p or JAK2, and cell viability, lactate dehydrogenase cytotoxicity, and cell mineralization were subsequently examined. The relationship between miR-211-5p and JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway was analyzed, and the targeting of miR-211-5p and JAK2 was also verified. The experimental results found that Eupatilin improved the pathological conditions of osteoporotic rats by promoting the proliferation and mineralization of osteoblasts. miR-211-5p was down-regulated and JAK2/STAT3 were up-regulated in osteoporotic rats. Upregulation of miR-211-5p further improved the pathological conditions of osteoporotic rats based on Eupatilin treatment. MiR-211-5p inhibited the JAK2/STAT3 pathway. Upregulation of JAK2 reversed the effects of elevated miR-211-5p on osteoporotic rats. Overall, Eupatilin attenuates postmenopausal osteoporosis through elevating miR-211-5p and repressing JAK2/STAT3 pathway.