apelin-13-peptide and Osteoporosis

Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-α phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.

Topics: AMP-Activated Protein Kinases; Animals; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cells; Mitophagy; Osteogenesis; Osteoporosis; Oxidative Stress; Rats; Signal Transduction

Adipokines play key roles in the regulation of obesity, type 2 diabetes mellitus, and bone growth. As a newly discovered hormone in the adipokines family, the precise role of Apelin-13 on bone metabolism is not yet clear. Apelin-13 and 25(OH)D3 expression were detected in freshly isolated serum of healthy individuals and osteoporosis patients with ELISA method. Apelin-13 deficient mice were set up and cortical bone geometry was measured with micro-computed tomography (Micro-CT) at 5 months old, then profile of organic bone matrix genes was detected with quantitative Real-Time PCR (qRT-PCR). Wnt/β-catenin signaling molecules were assayed in primary osteocytes isolated from neonatal calvarias. Apelin-13 and 25(OH)D3 showed decreased expression in osteoporosis patients. Five-month-old Apelin deficient mice exhibited decreased total and bone marrow cavity area and periosteal and endocortical bone surface. Deficiency of Apelin-13 downregulated collagen maturation associated genes (loxl3 and loxl4) and Wnt/β-catenin signaling, while loxl2 was upregulated, all of which indicated that Apelin-13 could play a role in regulating skeletal homeostasis. The decrease in bone formation in Apelin-13 deficient mice is associated with downregulation of organic bone matrix genes and Wnt/β-catenin signaling molecules, all of these indicate that association of Apelin-13 with bone mineral density (BMD) could be mediated by Wnt/β-catenin pathway.

Topics: Animals; beta Catenin; Bone Matrix; Cortical Bone; Humans; Intercellular Signaling Peptides and Proteins; Mice; Osteoporosis; Signal Transduction; Wnt Signaling Pathway