Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

Abstract

Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic bone resorption and osteoblastic bone formation. Estrogen deficiency causes bone loss and postmenopausal osteoporosis, the pathogenesis of which also involves oxidative stress, inflammatory processes, and the dysregulation of the expression of microRNAs (miRNAs) that control gene expression at post-transcriptional levels. Oxidative stress, due to an increase in reactive oxygen species (ROS), proinflammatory mediators and altered levels of miRNAs enhance osteoclastogenesis and reduce osteoblastogenesis through mechanisms involving the activation of MAPK and transcription factors. The present review summarizes the principal molecular mechanisms involved in the role of ROS and proinflammatory cytokines on osteoporosis. Moreover, it highlights the interplay among altered miRNA levels, oxidative stress, and an inflammatory state. In fact, ROS, by activating the transcriptional factors, can affect miRNA expression, and miRNAs can regulate ROS production and inflammatory processes. Therefore, the present review should help in identifying targets for the development of new therapeutic approaches to osteoporotic treatment and improve the quality of life of patients.

Keywords: bone remodeling; inflammatory mediators; miRNAs; osteoporosis; oxidative stress.

Figure 1

Principal molecular factors involved in the role of oxidative stress on osteoclastic and osteoblastic differentiation. Abbreviations: Nrf2, nuclear factor erythroid-2 related factor; MAPKs, mitogen-activated protein kinases; NF-kB, nuclear factor kappa B; NAFATc1, nuclear factor of activated T-cell cytoplasmic 1; TRAF-6, TNF receptor associated factor 6; KLF5, Krüppel-like factor 5; TP53INP2, tumor protein p53-inducible nuclear protein 2; mTor, mammalian target of rapamycin; FOXO, forkead proteins; (−) downregulated; (+) upregulated.