Micro-RNA in bone inhibition: A critical scoping review

Abstract

Bone formation is governed by a complex regulatory network in which osteoblast differentiation and activity are tightly controlled by transcriptional, epigenetic, metabolic, and mechanical cues. Among these regulatory layers, microRNAs (miRNAs) have emerged as critical post-transcriptional modulators that fine-tune osteogenic signaling. Increasing evidence demonstrates that a distinct subset of miRNAs functions as potent endogenous inhibitors of bone formation by directly targeting essential osteogenic genes, including RUNX2, ATF4, SMADs, β-catenin, BMP receptors, and mitochondrial regulators, and by converging on pathways such as Wnt/β-catenin, BMP/Smad, TGF-β, mechanotransduction, and mitochondrial homeostasis. Furthermore, inhibitory miRNAs operate not only within osteoblast lineage cells but also through intercellular communication, particularly via osteoclast- and MSC-derived exosomes that transfer anti-osteogenic miRNAs to recipient cells, thereby coupling resorption to suppressed bone formation. This article curates miRNAs that act as bone-formation inhibitors, providing a reference of their targets, pathways, and outcomes, and highlights their potential translational utility as therapeutic agents in conditions where suppression of bone formation is desirable, such as heterotopic ossification, fibrodysplasia ossificans progressiva, and pathological bone overgrowth.