Melatonin Accelerates Osteoporotic Bone Defect Repair by Promoting Osteogenesis–Angiogenesis Coupling

• DOI: 10.3389/fendo.2022.826660
• Publication Date: 2022-02-22T07:02:51Z
• Authors: Sheng Zheng; Chunhao Zhou; Han Yang; Junhua Li; Ziyu Feng; Liqing Liao; Yikai Li
• Keywords: Vascular Endothelial Growth Factor A; 0301 basic medicine; bone marrow mesenchymal stem cells; melatonin; Cell Differentiation; bone defect repair; RC648-665; osteoporosis; Diseases of the endocrine glands. Clinical endocrinology; Rats; 3. Good health; 03 medical and health sciences; Endocrinology; Osteogenesis; Animals; Osteoporosis; osteogenesis–angiogenesis coupling; Melatonin

Previous studies have revealed that melatonin could play a role in anti-osteoporosis and promoting osteogenesis. However, the effects of treatment on osteoporotic bone defect mechanism underlying angiogenesis are still unclear. Our study was aimed to investigate potential defect. Bone marrow mesenchymal stem cells (BMSCs) were isolated from femur tibia rats. The BMSC osteogenic ability assessed using alkaline phosphatase (ALP) staining, alizarin red S qRT-PCR, western blot, immunofluorescence. BMSC-mediated angiogenic potentials determined enzyme-linked immunosorbent assay, immunofluorescence, scratch wound transwell migration tube formation assay. Ovariectomized (OVX) rats with used establish an model then treated melatonin. OVX analyzed micro-CT, histology, sequential fluorescent labeling, biomechanical test. showed promoted both osteogenesis vitro . BMSCs indicated higher expression levels osteogenesis-related markers [ALP, osteocalcin (OCN), runt-related transcription factor 2, osterix] angiogenesis-related [vascular endothelial growth (VEGF), angiopoietin-2, angiopoietin-4] compared untreated group. Significantly, not able facilitate human umbilical vein cell directly, but it possessed promote by upregulating VEGF levels. In addition, we further found increased mineralization around control Immunohistochemical staining marker (OCN) (VEGF CD31) melatonin-treated Then, also strength rats, ultimate load stiffness, as performed three-point bending conclusion, our demonstrated osteogenesis–angiogenesis coupling. We accelerate repair These findings may provide evidence for application