First Author | Mao Z | Year | 2019 |
Journal | IUBMB Life | Volume | 71 |
Issue | 12 | Pages | 1916-1928 |
PubMed ID | 31317664 | Mgi Jnum | J:298467 |
Mgi Id | MGI:6480150 | Doi | 10.1002/iub.2131 |
Citation | Mao Z, et al. (2019) MicroRNA-155 inhibition up-regulates LEPR to inhibit osteoclast activation and bone resorption via activation of AMPK in alendronate-treated osteoporotic mice. IUBMB Life 71(12):1916-1928 |
abstractText | 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-alpha and IL-1beta 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-alpha, IL-1beta, 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. |