Cross-talk of MicroRNA and hydrogen sulfide: A novel therapeutic approach for bone diseases.

Bone homeostasis requires a balance between the bone formation of osteoblasts and bone resorption of osteoclasts to maintain ideal bone mass and bone quality. An imbalance in bone remodeling processes results in bone metabolic disorders such as osteoporosis. Hydrogen sulfide (H2S), a gasotransmitter, has attracted the focus of many researchers due to its multiple physiological functions. It has been implicated in anti-inflammatory, vasodilatory, angiogenic, cytoprotective, anti-oxidative and anti-apoptotic mechanisms. H2S has also been shown to exert osteoprotective activity through its anti-inflammatory and anti-oxidative effects. However, the underlying molecular mechanisms by which H2S mitigates bone diseases are not completely understood. Experimental evidence suggests that H2S may regulate signaling pathways by directly influencing a gene in the cascade or interacting with some other gasotransmitter (carbon monoxide or nitric oxide) or both. MicroRNAs (miRNAs) are short non-coding RNAs which regulate gene expression by targeting, binding and suppressing mRNAs; thus controlling cell fate. Certainly, bone remodeling is also regulated by miRNAs expression and has been reported in many studies. MicroRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new possibility for exploring the H2S-microRNA crosstalk in bone diseases. However, the relationship between miRNAs, bone development, and H2S is still not well explained. This review focuses on miRNAs and their roles in regulating bone remodeling and possible mechanisms behind H2S mediated bone loss inhibition, H2S-miRNAs crosstalk in relation to the pathophysiology of bone remodeling, and future perspectives for miRNA-H2S as a therapeutic agent for bone diseases.