MicroRNA‐155 inhibition up‐regulates LEPR to inhibit osteoclast activation and bone resorption via activation of AMPK in alendronate‐treated osteoporotic mice

Osteoporosis is characterized by a progressive increase in bone fragility, leading to low bone mass and structural deterioration of bone tissue. MicroRNA‐155 (miR‐155) is highly expressed in osteoporosis. Thus, the current study aimed to investigate the effect of miR‐155 on the inhibition of osteoclast activation and bone resorption by targeting leptin receptor (LEPR) through the adenosine monophosphate activated protein kinase (AMPK) pathway in alendronate‐treated osteoporotic mice. An osteoporosis mouse model was established to examine the bone tension and bone density and the expression of miR‐155 in osteoclasts. Binding sites between miR‐155 and LEPR were verified. Osteoclasts in the treatment group were transfected with different mimic, inhibitor, vector, or siRNA for subsequent experiments. The expression of miR‐155, LEPR, AMPK, p‐AMPK, RANKL, OPG, M‐CSF, RANK, TRAP, Bax, Bcl‐2, and the contents of TNF‐α and IL‐1β were all examined. The proliferation and bone resorption of osteoclasts were also detected. Mice with osteoporosis exhibited decreased bone density and bone tension, along with elevated expression of miR‐155. LEPR was verified as a target gene of miR‐155. Down‐regulated miR‐155 was found to increase the expression of LEPR, AMPK, p‐AMPK, OPG, Bax, decrease expression of TNF‐α, IL‐1β, RANKL, M‐CSF, RANK, TRAP, Bcl‐2, inhibit the cell proliferation and bone resorption of osteoclasts. Taken together, decreased miR‐155 up‐regulated LEPR via activation of AMPK, which ultimately repressed osteoclast activation and bone resorption of osteoclasts in alendronate‐treated osteoporotic mice.