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

Abstract

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.

RETRACTED ARTICLE: The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide

“…In other rodent models of lung pathology, endogenous H 2 S has been suggested to have a protective role of anti-inflammation and bronchodilation in chronic cigarette smoke-induced pulmonary injury in rats [ 49 ], and H 2 S provokes tachykinin-mediated neurogenic inflammation that is mediated by stimulation of TRPV1 receptors on the sensory nerve endings in Guinea Pigs [ 50 ]. Furthermore, considering the emergence of data suggesting a degree of cross-talk between H 2 S and epigenetic modifiers such as miRNAs [ 51 , 52 ], and our own data suggesting broadly different epigenetic profiles between lung pathologies (including COPD) in ASM [ 4 , 9 , 10 , 12 , 13 ]. Hence, the difference between a COPD ASM cell and a ‘healthy’ ASM cell may incorporate one, or more likely, more of these H2S targets/activators.…”

MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2

“…3C). To confirm these findings, the caspase-3 activity was also detected as a common marker for apoptosis (9,31). A consistent result further suggested that the overexpression of miR-497 induced apoptosis by markedly increasing the caspase-3 activity (~2.2 fold) (Fig.…”

“…They are considered to function as mRNA regulators by interacting with the 3'-untranslated region (3'UTR) of the targeted mRNA transcript and leading to degradation (2)(3)(4)(5). Several, if not all, biological processes are reported to be regulated by miRNAs, including cell cycle, proliferation, metabolism, immune response, hematopoiesis and differentiation (6)(7)(8)(9)(10). It is widely accepted that miRNAs are vital in the process of tumorigenesis by targeting key factors (11,12).…”

“…Its expression is also considered to be regulated by multiple miRNAs, including miR-497. Bcl-2 family proteins are also involved in the chemoresistance of MM (9).…”

Hydrogen Sulfide: A Worthwhile Tool in the Design of New Multitarget Drugs

“…Recent studies on physiological and pathophysiological roles of H 2 S, revealed its therapeutic potential in bone diseases (Liu et al, 2014 ; Zhai et al, 2017 ).…”