Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review

Abstract

MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3′-untranslated regions (3′-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/β-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-βs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-β/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.

Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis)

“…Other local mediations of ectopic calcifications are bone morphogenic proteins (BMP) and bone-derived growth factors [ 41 , 99 , 100 , 101 ]. BMP-5 expression increases during chondrocyte differentiation in vivo and in vitro, and it promotes proliferation and cartilage matrix synthesis in primary chondrocyte cultures [ 102 , 103 , 104 ]. On the contrary, CCN [cysteine-rich angiogenic protein 61 (CCN1/CYR61), connective tissue growth factor (CCN2/CTGF), and nephroblastoma overexpressed (CCN3/NOV)] family, particularly, CCN2/CTGF stands for an atypical growth factor for chondrocytes/cartilages that prevents local hypertrophy or calcification, and local defects of this system might be involved in abnormal calcium deposits [ 105 ].…”

Review on the protective activity of osthole against the pathogenesis of osteoporosis

“…BMP-2 and TGFβ promote the osteogenic and tenogenic differentiation of ligament-derived stem cells (LDSCs) ( Wei et al, 2023 ). However, TGF-β and BMP signaling pathways are antagonized by different components ( Loh et al, 2023 ). One study reports that osthole can reduce the expression of TGFβ, Smad2, and Smad3 and block TGFβ-induced Smad2/3 phosphorylation and nuclear translocation ( Liu et al, 2018 ; Yue et al, 2020 ).…”

Regulation of bone homeostasis: signaling pathways and therapeutic targets

“… 112 In the early stage of osteoblast proliferation and differentiation, TGF‐β initiates the osteogenic process by promoting the proliferation of osteoprogenitor cells. 113 It does this by activating the SMAD2/3 signaling pathway. Once activated, SMAD2 and SMAD3 translocate to the nucleus, where they influence the transcription of key osteogenic genes.…”