LINC00323 induced by hypoxia promote cartilage callus by interacting with FUS to regulate PDGFB expression

Abstract

Intermittent hypoxia has been reported to contribute beneficial effects on fracture healing depending on various factors like duration, frequency, and severity. Yet, little is known about the underlying molecular mechanism. Our previous study found that LINC00323 was up-regulated under hypoxic conditions, suggesting that it might play a final role in hypoxia-induced fracture repair. The present study is to investigate the osteogenic effect of LINC00323 in vitro and in vivo. Upregulation of LINC00323 enhanced the mineralization and activity ALP and increased the expression of osteogenic markers. Further analysis revealed that LINC00323 promoted PDGFB expression by binding FUS to regulate the growth and osteogenic differentiation of MC3T3-E1. Lentivirus mediated LINC00323 particles were injected into the fracture site of the tibia of mice, and fracture healing was evaluated by X-rays, micro-CT examination, biomechanical test and histological staining. Local injection of Lentivirus-LINC00323 increased bone mass, biomechanical strength and cartilage callus formation. These findings indicated that LINC00323 induced the differentiation of osteoblast-like cells via regulation of the expression of PDGFB, represents a theoretical basis to accelerate fracture healing.