Leptin Overexpression in Bone Marrow Stromal Cells Promotes Periodontal Regeneration in a Rat Model of Osteoporosis

Zheng, Baoyu; Jiang, Jun; Chen, Yuling; Lin, Minkui; Du, Zhibin; Xiao, Yin; Luo, Kai; Yan, Fuhua

doi:10.1902/jop.2017.170042

Cited by 31 publications

(41 citation statements)

References 50 publications

(57 reference statements)

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“…The current study provides researchers with a basic, but refine able procedure of how to regenerate tissue. Attempts have already been made to improve the scaffolds with, for example, nano‐particles to enhance osteogenic metabolic activity and thus tissue regeneration, or adding active molecules to the BMSC sheets (e.g., autologous platelet‐rich plasma), or gene transfection (e.g., adenoviruses harboring the human [h]LEP gene) …”

Section: Discussionmentioning

confidence: 99%

Enhancing bone regeneration by combining mesenchymal stem cell sheets with β‐TCP/COL‐I scaffolds

Lin

Shao

et al. 2017

J Biomed Mater Res

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The combination of bone marrow-derived mesenchymal stem cells (BMSCs) and biological scaffolds has been demonstrated to be a promising strategy for bone regeneration. However, this method does not result in satisfactory bone regeneration, because the BMSCs are dispersed in the biological scaffolds. The current study developed a new bone regeneration system, which combines synthetic porous three-dimensional scaffolds of β-TCP/COL-I composite with cultured osteogenic sheets of BMSCs. Activity of alkaline phosphatase (ALP), a marker of bone regeneration, was assayed in vitro using enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction. In vivo bone regeneration was assayed in male nude mice. The study samples were BMSC sheet, scaffold/scattered BMSCs, scaffold/BMSC sheet, and scaffold alone. The samples were implanted dorsally in the mice. In vitro analysis showed that β-TCP/COL-I scaffold combined with BMSC sheets significantly upregulated both gene expression and protein levels of ALP, osteocalcin, and osteopontin. Histological and micro-computed tomography showed that the only implants that demonstrated new bone formation after 4 weeks were scaffold/BMSC sheet implants. These results underscore the crucial requirement of a synergistic effect of β-TCP/COL-I scaffolds and BMSC sheets. This could be a promising novel strategy for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2037-2045, 2018.

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Section: Discussionmentioning

confidence: 99%

Enhancing bone regeneration by combining mesenchymal stem cell sheets with β‐TCP/COL‐I scaffolds

Lin

Shao

et al. 2017

J Biomed Mater Res

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“…Several studies also demonstrated that a leptin‐deficient mouse model has reduced bone mineral content of long bones, and systemic leptin administration usually exerts a positive effect on bone mass or promoting fracture healing (Reid et al, ; Wu, Shao, Dass, & Wei, ). Leptin deficiency was reported to be associated with increased marrow adipose tissue and reduced bone formation (Lindenmaier et al, ); meanwhile, leptin overexpression promoted the bone differentiation in hBMSCs (Xu, Wu, Zhou, Yang, & Liu, ; Zheng et al, ). Therefore, the balance between APN and leptin secretion, which may also contribute to conflicting results in this field.…”

Section: Discussionmentioning

confidence: 99%

Effect of adiponectin secreted from adipose‐derived stem cells on bone‐fat balance and bone defect healing

Yang

Liu

et al. 2019

J Tissue Eng Regen Med

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The efficacy of adiponectin (APN) in regulating bone metabolism remains controversial. This study aimed to investigate the role of APN secreted from adipose-derived stem cells on adipogenesis and osteogenesis. Human APN gene was transfected via recombinant adenovirus into adipose derived stem cells (ASCs) in vitro and were cocultured with bone marrow mesenchymal stem cells (BMSCs) in using a transwell chamber. Adipogenesis was inhibited in APN-transfected ASCs; in BMSCs, adipogenesis was inhibited, but osteogenesis was promoted in coculture with APN-transfected ASCs. Next, the same adenovirus construct was transfected into the abdominal adipose tissue of a Sprague Dawley rat in vivo, and then a tibia defect was established in the same rat. We confirmed there was higher gene and protein expression of APN in ASCs and the abdominal adipose tissue of these rat models. Development of adipocytes in abdominal adipose tissue was suppressed, and less new bone was formed in the bone defect area. In conclusion, APN secreted from ASCs could directly inhibit adipogenesis in ASCs and BMSCs and promote osteogenesis in the latter.However, APN overexpression in adipose tissue was inversely associated with bone formation in tibia defects potentially due to decreased levels of circulating boneactivating hormones.

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“…Tariq et al (43) found that body weight and body mass index impact BMD, whereas serum leptin is not associated with BMD. Zheng et al (44) identified that LEP overexpression in bone marrow stromal cells can stimulate periodontal regeneration in osteoporotic conditions. The association between LEP and OP is unclear, and should be a focus of future studies.…”

Section: Discussionmentioning

confidence: 99%

Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach

Chai

Tan

et al. 2018

Oncol Lett

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Osteoporosis (OP) is an age-related disease, and osteoporotic fracture is one of the major causes of disability and mortality in elderly patients (>70 years old). As the pathogenesis and molecular mechanism of OP remain unclear, the identification of disease biomarkers is important for guiding research and providing therapeutic targets. In the present study, core genes and microRNAs (miRNAs) associated with OP were identified. Differentially expressed genes (DEGs) between human mesenchymal stem cell specimens from normal osseous tissues and OP tissues were detected using the GEO2R tool of the Gene Expression Omnibus database and Morpheus. Network topological parameters were determined using NetworkAnalyzer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, and ClueGO. Cytoscape with the Search Tool for the Retrieval of Interacting Genes and Molecular Complex Detection plug-in was used to visualize protein-protein interactions (PPIs). Additionally, miRNA-gene regulatory modules were predicted using CyTargetLinker in order to guide future research. In total, 915 DEGs were identified, including 774 upregulated and 141 downregulated genes. Enriched GO terms and pathways were determined, including 'nervous system development', 'regulation of molecular function', 'glutamatergic synapse pathway' and 'pathways in cancer'. The node degrees of DEGs followed power-law distributions. A PPI network with 541 nodes and 1,431 edges was obtained. Overall, 3 important modules were identified from the PPI network. The following 10 genes were identified as core genes based on high degrees of connectivity: Albumin, PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2), DNA topoisomerase 2-α, kininogen 1 (KNG1), interleukin 2 (IL2), leucine-rich repeats and guanylate kinase domain containing, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG), leptin, transferrin and RNA polymerase II subunit A (POLR2A). Additionally, 15 miRNA-target interactions were obtained using CyTargetLinker. Overall, 7 miRNAs co-regulated IL2, 3 regulated PHLPP2, 3 regulated KNG1, 1 regulated PIK3CG and 1 modulated POLR2A. These results indicate potential biomarkers in the pathogenesis of OP and therapeutic targets.

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Leptin Overexpression in Bone Marrow Stromal Cells Promotes Periodontal Regeneration in a Rat Model of Osteoporosis

Abstract: hLEP overexpression in BMSCs can stimulate periodontal regeneration in osteoporotic conditions and might be a promising strategy for periodontal regeneration in patients with osteoporosis.

Cited by 31 publications

References 50 publications

Enhancing bone regeneration by combining mesenchymal stem cell sheets with β‐TCP/COL‐I scaffolds

Enhancing bone regeneration by combining mesenchymal stem cell sheets with β‐TCP/COL‐I scaffolds

Effect of adiponectin secreted from adipose‐derived stem cells on bone‐fat balance and bone defect healing

Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach

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