Effect of adipokines on bone marrow mesenchymal stem cell function

Figure 2 The mechanism by which adipokines regulate the proliferation, apoptosis, and differentiation of bone marrow-derived mesenchymal stem cells. Adipokines produced by adipose tissue regulate the osteogenic, adipogenic, and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) through various signaling pathways, and affect BMSC apoptosis and proliferation processes. Visfatin enhances osteogenic differentiation by up-regulating runt-related transcription factor 2 expression, and can delay cell aging through NAD+-sirtuin 1-p53. Chemerin regulates BMSC chemotaxis, proliferation, migration and osteogenic differentiation through chemerin chemokine-like receptor 1 and may regulate cartilage differentiation through extracellular regulated protein kinases 1/2 pathway. Vaspin specifically activates phosphoinositide-3 kinase/protein kinase B and extracellular regulated protein kinases 1/2 signaling pathways, inhibits inflammatory signaling pathways such as nuclear factor kappa B, and activates mitogen-activated protein kinase/p38 signaling pathways, thus enhancing BMSC viability, proliferation, differentiation, anti-apoptosis and anti-inflammatory ability. Adiponectin activates peroxisome proliferator-activated receptor γ pathway, stem cell factor/signal transducer and activator of transcription 3/hypoxia inducible factor 1α pathway, stromal cell-derived factor 1/CXC receptor 4, adenosine 5’-monophosphate-activated protein kinase pathway and Wnt/β-catenin through Adiponectin receptor 1 to promote BMSC migration, apoptosis and differentiation. IL-6/8: Interleukin-6/8; MCP-1: Monocyte chemotactic protein-1; MMP2/13: Matrix metalloproteinases 2/13; NAD: Nicotinamide adenine dinucleotide; Sirt1: Sirtuin 1; AKT: Protein kinase B; GSK3β: Glycogen synthase kinase 3 beta; CMKLR1: Chemokine-like receptor 1; ERK: Extracellular regulated protein kinases; PI3K: Phosphoinositide-3 kinase; MAPK: Mitogen-activated protein kinase; RUNX2: Runt-related transcription factor 2; Bcl-2: B cell lymphoma-2; SDF-1: Stromal cell-derived factor 1; CXCR4: CXC receptor 4; SCF: Stem cell factor; STAT3: Signal transducer and activator of transcription 3; HIF1α: Hypoxia inducible factor 1α; AMPK: Adenosine 5’-monophosphate-activated protein kinase; APN: Adiponectin; APPL1: Adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1; Acc: Acetyl-CoA carboxylase; BMP2: Bone morphogenetic protein 2; BMSCs: Bone marrow mesenchymal stromal cells.