Bone morphogenetic protein-2 exhibits therapeutic benefits for osteonecrosis of the femoral head through induction of cartilage and bone cells

Abstract

Osteonecrosis of the femoral head is an orthopedic disease caused by femoral head damage or insufficient blood supply, which leads to the death of bone cells and bone marrow. Osteonecrosis of the femoral head leads to changes in the structure of the femoral head, femoral head collapse and joint dysfunction. Bone morphogenetic protein-2 (BMP-2) exhibits beneficial effects on bone formation, repair and angiogenesis at the femoral head. In the present study, the therapeutic effects of recombinant human BMP-2 containing an Fc fragment (rBMP-2/Fc) were investigated on a steroid induced mouse model of osteonecrosis of the femoral head. Bone cell viability was used to determine the in vitro effects of rBMP-2/Fc. The therapeutic efficacies of rBMP-2/Fc on mice with osteonecrosis of the femoral head were evaluated using clinical arthritis scores. The expression levels of inflammatory factors in the mice were analyzed by reverse transcription-quantitative polymerase chain reaction. Histological analysis was used to evaluate the effects of rBMP-2/Fc on the femoral head. The results revealed that rBMP-2/Fc treatment significantly increased the IL-6, IL-10, vascular endothelial growth factor and macrophage colony-stimulating factor expression levels in synovial cells compared with the control group (P<0.01). Furthermore, it was observed that rBMP-2/Fc significantly improved the viability and growth of synovial cells (P<0.01) through the nuclear factor (NF)-κB signaling pathway. Treatment with rBMP-2/Fc significantly decreased receptor activator of NF-κB ligand expression levels. Furthermore, in vivo experiments demonstrated that rBMP-2/Fc treatment markedly relieved the arthralgia and damage caused by osteonecrosis of the femoral head. In conclusion, rBMP-2/Fc treatment may be beneficial for articular cartilage repair by the upregulation of angiogenesis factors through the down regulation of the NF-κB signaling pathway in mice with osteonecrosis of the femoral head. This preclinical data suggests that rBMP-2/Fc may be a promising novel agent for treatment of osteonecrosis of the femoral head.

Expression of The Factors Associated With Wnt/β-Catenin, BMP-2/Runx2/Osterix, OPG/RANKL&nbsp;and&nbsp;LGR4/RANKL Pathways&nbsp;in Postmenopausal Osteoporosis Fracture

“…Kaback's [32] study showed that after the fracture model in mice was established, cartilage and tissue started to form after 7 days and sustained 10 days, meanwhile the mRNA level of Sox9 increased; Osterix was mainly expressed in the osteoblast near the site of fracture about 14 days later, meanwhile the expression of sox9 decreased, during this time cartilage became hard bone at the injured place. Numerous studies and clinical manifestations con rmed that BMP had unique osteogenic effect, and ber junction was completed at at 2 weeks' time after fracture [8,9] . The level of Osterix in BMP-2/Runx2/Osterix pathway appeared the lowest in group D (8-14 days), which was consistent with above study.…”

“…PMOP is due to the rapid decline in estrogen levels in women after menopause and osteoclast resulting in a signi cant increase in bone resorption, while osteoblasts did not increase synchronously, resulting in bone resorption greater than bone formation, it's a metabolic disease [12] . The classical Wnt/β-catenin, BMP-2/Runx2/Osterix, OPG/RANKL and LGR4/RANKL/RANK signaling pathways play important roles in regulating osteogenesis and osteoclastogenesis [6][7][8][9][10][11] . Based on histological observation and molecular studies of fracture healing, the early stage of fracture healing is divided into early in ammatory response stage (within 1 days after fracture), non-speci c anabolic stage (within 3 days after fracture), non-speci c catabolism stage (3 days to 1 week after fracture) and more speci c anabolic stage of bone tissue ( 1week after fracture); while the typical fracture healing stage was divided into three stages: hematoma organization stage (2-3 weeks after fracture), original callus formation stage (4-6 weeks after fracture), callus reconstruction molding stage (more than 1 years after fracture) [13][14] .…”

“…The classical Wnt/β-catenin, BMP-2/Runx2/Osterix, OPG/RANKL and LGR4/RANKL signaling pathways play important roles in regulating osteogenesis and osteoclastogenesis. LRP5, β-catenin, Runx2, C-myc, Runx2 and Osterix are key osteogenic factors, while OPG, RANKL, LGR4 and RANKL are key related osteoclast factors [6][7][8][9][10][11] . In this study, RT-qPCR was used to compare the expression of LRP5, β-catenin, Runx2, C-myc, Osterix, OPG, RANKL and LGR4 in bone tissues of PMOPF patients and postmenopausal patients with other types of fracture (control group).…”

Up-Regulation of Urinary Exosomal Hsa-microRNA-200b-3p and Hsa-microRNA-206 in Patients of Steroid-induced Osteonecrosis of Femoral Head

“…The TGF-β signaling pathway plays a fundamental role in embryonic skeletal development and postnatal bone homeostasis [29]. Similar to other TGF-β family proteins, bone morphogenetic protein 2 (BMP-2) has been implicated in the pathogenesis of SONFH and has therapeutic bene ts for SONFH by inducing bone cells and cartilage [30]. The coupling of angiogenesis, dead bone absorption and new bone formation is a crucial link in the repair of femoral head necrosis.…”

The combination of PLLA/PLGA/PCL composite scaffolds integrated with BMP‑2‑loaded microspheres and low‑intensity pulsed ultrasound alleviates steroid‑induced osteonecrosis of the femoral head

“…Of note, the BMP family of proteins, including BMP-2, BMP-4 and BMP-7, have the potential to induce endochondral bone formation when implanted into mammals ( 11 ). BMP-2 has been previously demonstrated to be an osteoconductive growth factor beneficial for ONFH by promoting cartilage repair and inducing osteoblast proliferation or differentiation ( 12 ). Recombinant human BMP-2 (rhBMP-2) may improve the clinical efficacy of impacted bone graft surgery by enhancing bone repair in ONFH ( 13 ).…”