mir-21 Overexpressing Mesenchymal Stem Cells Accelerate Fracture Healing in a Rat Closed Femur Fracture Model

Abstract

MicroRNAs are small noncoding RNAs involved in numerous biological processes. Emerging pieces of evidence suggest that microRNAs play important roles in osteogenesis and skeletal homeostasis. Recent studies indicated the significant regulation function of mir-21 in osteogenesis in vitro, but little information is known about its veritable functions in vivo. In the present study, we aimed to investigate the effect of mir-21 intervention on osteogenic differentiation of rats bone marrow derived mesenchymal stem cells (rBMSCs) and repair capacity in rats closed femur fracture model with internal fixation. The results showed that the upregulation of mir-21 not only increased the expression of osteopontin and alkaline phosphatase in rBMSCs but also promoted mineralization in the condition of osteogenic induction. Furthermore, the bone healing properties were also improved in fracture healing model according to the results of micro-CT, mechanical test, and histological analysis. The current study confirms that the overexpression of mir-21 could promote osteogenesis and accelerate bone fracture healing, which may contribute to a new therapeutic way for fracture repair.

Icariin attenuates titanium particle‐induced inhibition of osteogenic differentiation and matrix mineralization via miR‐21‐5p

“…In addition, icariin can also induce osteoclast apoptosis and inhibit differentiation of osteoclasts and bone resorption (Zhang et al, ). MicroRNAs (miRNAs), a class of small non‐coding RNAs of approximately 22 nucleotides that post‐transcriptionally regulate target mRNAs, have been reported to promote osteoblast differentiation, including miR‐21 (Meng et al, ; Sun et al, ; Wei et al, ; Li et al, ). Accumulating evidence has revealed the stimulatory effect of miR‐21 on osteoblastic differentiation (Meng et al, ; Sun et al, ; Wei et al, ; Li et al, ).…”

The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

“…Using systemic downregulation of miR‐92a (via antimir‐92a) in a mouse femoral fracture model, the authors found increased callus volume and neovascularization that resulted in enhanced fracture repair (Figure ) . Sun et al engineered miR‐21 overexpressing bone marrow–derived mesenchymal stem cells (BMSCs) and injected these cells into the fracture site of rat transverse femoral fractures. At 7 days postfracture, they observed accelerated endochondral ossification, greater bone volume, and ultimately a biomechanically stronger bone.…”

“…At 7 days postfracture, they observed accelerated endochondral ossification, greater bone volume, and ultimately a biomechanically stronger bone. Given their data, the authors suggested that this may be a potential therapeutic approach to enhance fracture repair …”

MiR‐148a regulates bone marrow mesenchymal stem cells‐mediated fracture healing by targeting insulin‐like growth factor 1

“…Then, osteoblasts and chondrocytes calcify and develop into immature bone. Ultimately, bone remodeling is activated together with osteoclasts . In light of this knowledge, exogenous intervention of BMSCs in fracture healing has been reported to be feasible.…”