AAV-Anti-miR-214 Prevents Collapse of the Femoral Head in Osteonecrosis by Regulating Osteoblast and Osteoclast Activities

Abstract

Osteonecrosis of the femoral head, an intractable but common disease that eventually triggers collapse of the femoral head, is characterized by increased osteoclast activity and markedly decreased osteoblast activity in the necrotic region of the femoral head. MicroRNA (miRNA)-214 (miR-214) may play important roles in vertebrate skeletal development by inhibiting osteoblast function by targeting activating transcription factor 4 (ATF4) and promoting osteoclast function via phosphatase and tensin homolog (PTEN). This study revealed significantly increased levels of miR-214 in necrotic regions, with commensurate changes in the numbers of its target cells (both osteoblasts and osteoclasts). To investigate whether targeting miR-214 could prevent femoral head collapse, we constructed an adeno-associated virus (AAV)-associated anti-miR-214 (AAV-anti-miR-214) and evaluated its function in vivo. AAV-anti-miR-214 promoted osteoblast activity and diminished osteoclast activity, effectively preventing collapse of the femoral head in a rat model of osteonecrosis.

microRNA‐148a‐3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head

“…ONFH, as one of common and intractable diseases, results in the collapse of the femoral head ultimately, accompanied by the decrease of osteoblast activity in the region of ONFH. 21 EVs derived from BMSCs were found to regulate steroid-induced osteonecrosis of the femoral head. 22 Additionally, miRs are involved in various bone diseases and play a role in the mechanism of ONFH.…”

The role of biomechanical forces and MALAT1/miR‐329‐5p/PRIP signalling on glucocorticoid‐induced osteonecrosis of the femoral head

“…Abnormal bone metabolism is one theory for the pathogenesis of GIONFH. Previous studies have usually focused on either osteoclasts or osteoblasts since these cells are regulated through different signalling pathways 10,22‐24 . Our study is the first to assess the effect of concurrent osteoclast and osteoblast differentiation on GIONFH through the expression of PRIP protein.…”

miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells

“…It is worth mentioning that miR-214 may serve as a potential target for small-molecule drug delivery systems. 32 Wang et al 33 have demonstrated that the function of osteoblast activity promotion was achieved by knockdown of miR-214 by adenoviral vectors in an osteonecrosis rat model. A parallel result was obtained by sponging miR-214 through baculovirus vector, and a combination of Bone Morphogenetic Protein 2 could promote the healing effect of bone synergistically.…”

“…34 The dual-regulatory function, including inhibiting osteoblast activity and enhancing osteoclast activity, of miR-214 may play an important role in regulating osteogenesis activities. 10,12,33 In addition, targeted materials loading with miR-214 may also have profound prospects. Sun et al 35 have designed polyurethane nanomicelles modified by osteoblast-targeting peptides as delivery systems to deliver antagomiR-214 to osteoblasts, which was proved to be successful in an ovariectomized osteoporosis mouse model, since bone mass and formation were improved significantly.…”