| First Author | Taipaleenmäki H | Year | 2022 |
| Journal | EMBO Mol Med | Volume | 14 |
| Issue | 11 | Pages | e13617 |
| PubMed ID | 36193848 | Mgi Jnum | J:346342 |
| Mgi Id | MGI:7383371 | Doi | 10.15252/emmm.202013617 |
| Citation | Taipaleenmaki H, et al. (2022) Antagonizing microRNA-19a/b augments PTH anabolic action and restores bone mass in osteoporosis in mice. EMBO Mol Med 14(11):e13617 |
| abstractText | Postmenopausal bone loss often leads to osteoporosis and fragility fractures. Bone mass can be increased by the first 34 amino acids of human parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), or by a monoclonal antibody against sclerostin (Scl-Ab). Here, we show that PTH and Scl-Ab reduce the expression of microRNA-19a and microRNA-19b (miR-19a/b) in bone. In bones from patients with lower bone mass and from osteoporotic mice, miR-19a/b expression is elevated, suggesting an inhibitory function in bone remodeling. Indeed, antagonizing miR-19a/b in vivo increased bone mass without overt cytotoxic effects. We identified TG-interacting factor 1 (Tgif1) as the target of miR-19a/b in osteoblasts and essential for the increase in bone mass following miR-19a/b inhibition. Furthermore, antagonizing miR-19a/b augments the gain in bone mass by PTH and restores bone loss in mouse models of osteoporosis in a dual mode of action by supporting bone formation and decreasing receptor activator of NF-kappaB ligand (RANKL)-dependent bone resorption. Thus, this study identifies novel mechanisms regulating bone remodeling, which opens opportunities for new therapeutic concepts to treat bone fragility. |
