The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression

Abstract

Osteoporosis is a complex multifactorial disorder linked to various risk factors and medical conditions. Bone marrow-derived mesenchymal stem cell (BMSC) dysfunction potentially plays a critical role in osteoporosis pathogenesis. Herein, the study identified that miR-4739 was upregulated in BMSC cultures harvested from osteoporotic subjects. BMSCs were isolated from normal and osteoporotic bone marrow tissues and identified for their osteogenic differentiation potential. In osteoporotic BMSCs, miR-4739 overexpression significantly inhibited cell viability, osteoblast differentiation, mineralized nodule formation, and heterotopic bone formation, whereas miR-4739 inhibition exerted opposite effects. Through direct binding, miR-4739 inhibited distal-less homeobox 3 (DLX3) expression. In osteoporotic BMSCs, DLX3 knockdown also inhibited BMSC viability and osteogenic differentiation. Moreover, DLX3 knockdown partially attenuated the effects of miR-4739 inhibition upon BMSCs. Altogether, the miR-4739/DLX3 axis modulates the capacity of BMSCs to differentiate into osteoblasts, which potentially plays a role in osteoporosis pathogenesis. The in vivo and clinical functions of the miR-4739/DLX3 axis require further investigation.

miR-141-3p Targeted SIRT1 to Inhibit Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

“…miRNA could bind to the 3 ′ UTR region of related genes to suppress its translation and then affect numerous biological processes [10,19]. Studies have confirmed that miRNAs are essential in BMSC osteogenic differentiation [20,21]. For example, in osteogenic differentiation, RUNX2 is a targeted regulatory gene of miR-135 [22].…”

Strategy of a cell-derived extracellular matrix for the construction of an osteochondral interlayer

“…53 While the sparse study has paid attention to using a D-ECM to modulate the hypertrophic differentiation of BMSCs, which is the main cell source for articular defect repairing as the multipotential cells migrate from the bone marrow cavity into the defect area. [54][55][56] It has been known that the CCL is a transition zone connecting the cartilage and bone parts, mainly containing hypertrophic chondrocytes that transform from chondrocytes and then are calcified to form osteoblasts. 57,58 It is suggested that the D-ECMs derived from osteoblasts, Cho, and HCho should all have a large or small effect on BMSC hypertrophy.…”

The mechanism of oxytocin and its receptors in regulating cells in bone metabolism

“…OB originate from BMSCs and are closely related to new bone formation, which are mainly responsible for the synthesis and secretion of bone matrix and the mineralization of bone matrix, thus playing a vital role in bone formation ( Li et al, 2021 ). POT is produced by OB in the bone marrow and acts as a paracrine–autocrine regulator of bone formation ( Elabd et al, 2008 ; Ein-Dor et al, 2018 ).…”