One of the promising approaches for osteoporosis treatment is bone regeneration. In this case, several therapeutic options can be considered, including: osteogenic differentiation of stem cells and expansion and maturation of osteoblasts. Many epigenetic mechanisms are involved in the modulation of bone regeneration, among them microRNAs (miRs) have been taken into great consideration. MiRs are small non-coding RNAs that exert fundamental regulating functions on multiple physiological and pathological processes as they target messenger RNAs for degradation or inhibit translation. An increasing number of miRs have been identified to play critical roles in bone remodeling which their expression is up/down regulated during osteogenesis, regulate osteoblast and osteoclast differentiation and function or participate in regulation of osteo-related signaling pathways. For example, miR-2861 and miR-335-5p promote osteoblast differentiation through activating of histone deactylase 5 or Wnt signaling. Runx2 has been confirmed as a direct target of miR-335. MiR-20a increases osteogenic differentiation of mesenchymal stem cells through upregulation of the BMP/Runx2 pathway. MiR-27 mediates osteoblast differentiation by directly inhibiting oncogene expression and activating Wnt signaling which in turn activates miR-29a. Other miRs; such as miR-21-5p, miR-31-5p, miR-133a-3p, Hsa-miR-422a, Hsa-miR-148a-3p, miR-183-5p, miR-214-3p, miR-223-3p, miR-9718, miR-138, miR-30, miR-542-3P, miR-34, miR-223, miR-194, miR-637, miR106a, miR-17-5P and miR-204 inhibitory or promote osteoclast formation. Conclusion: A better understanding of how miRs network participate in bone regeneration will provide us new targets for investigating clinical perspectives of osteoporosis treatment and preliminary applications of MiRs show promising evidence to serve as therapeutic targets for osteoporosis.

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