Expression of HIF‑1α in cycling stretch‑induced osteogenic differentiation of bone mesenchymal stem cells

Abstract

During orthodontic treatment, mechanical force is applied to the teeth, and following a series of complex metabolism changes, the position of the teeth in the alveolar bone change. This process is closely associated with primitive bone mesenchymal stem cells (BMSCs), which may differentiate into osteoblasts precursor cell. A hypoxic microenvironment may be caused by orthodontic mechanical forces between the alveolar bone and the root. Hypoxia-inducible factor 1α (HIF-1α) is a specific receptor that adapts to a hypoxic environment. The present study was designed to investigate whether HIF-1α was involved in the osteoblastic differentiation of BMSCs induced by cyclic tensile stress. During this process, HIF-1α mRNA and protein expression were detected using a reverse transcription-quantitative polymerase chain reaction and western blotting. It was revealed that alkaline phosphatase activity increased in a time-dependent manner in three different stretching strength groups, which indicates that cyclic stretch promotes the osteogenic differentiation of BMSCs. The optimal force stage of osteogenesis was an unexpected discovery, which will provide theoretical guidance for selecting the most suitable orthodontic force for tooth movement in clinical orthodontic treatment. Most importantly, all experiments revealed that HIF-1α mRNA and protein were significantly increased following stretching treatment in BMSCs. It was therefore concluded that HIF-1α may be involved in BMSCs modulating osteogenic metabolism during exposure to cyclic stretch and a hypoxic microenvironment, which may prove useful for the reconstruction of a jaw during orthodontic treatment.

A Novel Tension Machine Promotes Bone Marrow Mesenchymal Stem Cell Osteoblastic and Fibroblastic Differentiation by Applying Cyclic Tension

“…By using this device, we first investigated the suitable extension rate for BMSCs. According to similar preliminary experimental research methods, the elongation rate of the BMSC tension assay was mostly set to vary from 10% to 15% [ 11 , 12 ]. Considering that the force application method of iStrain may be different from that used by other researchers, we first set the extension rate to three values: 9%, 12%, and 15%.…”

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

“…Hypoxia and HIF-1α maintain the chondrogenic phenotype of cells by preventing cell osteogenic differentiation TWIST expression, which in turn decreases RUNX2 and BMP2 expression [119] and regulates BMSC osteogenic differentiation [120]. However, the effect of cyclic tensile stress on Hif-1α expression varies across the stretch range and, in turn, affects different osteogenic differentiation capacities [121]. HIF-1α can also mediate the expression of RUNX2 in PDLSCs through the induction of vascular endothelial growth factor (VEGF) upregulation and promote early osteogenic differentiation [122].…”

HIF-1α Regulates Bone Homeostasis and Angiogenesis, Participating in the Occurrence of Bone Metabolic Diseases

“…TWIST, as a transcriptional inhibitor of runt-related transcription factor 2 (RUNX2), is one of the downstream targets of HIF-1α, inhibiting BMSCs osteogenic differentiation by downregulating bone morphogenetic protein 2 (BMP2) and RUNX2 [ 57 , 58 , 59 , 60 , 61 , 62 ]. Mechano growth factor (MGF) is a splicing variant of insulin-like growth factor 1 (IGF-1), which can be used for autocrine tissue repair.…”