HGF/MET in osteogenic differentiation of primary human palatal periosteum-derived mesenchymal stem cells.

PURPOSE This study aimed to determine expressions of hepatocyte growth factor (HGF) and MET proto-oncogene receptor tyrosine kinase (MET) in palatal periosteum (PP) and to examine the effect of HGF/MET on osteogenic differentiation of human palatal periosteum-derived mesenchymal stem cells (PD-MSCs). METHODS HGF/MET proteins in human palatal periosteum (n = 3) were localized using immunohistochemistry. PD-MSCs (n = 3) were cultured in serum-free Essential 8 (E8) medium or osteogenic medium with and without Capmatinib, a selective ATP-inhibitor of MET. HGF concentration in vitro was measured with ELISA. Relative gene expression was quantified from PD-MSCs by quantitative reverse transcription real-time polymerase chain reaction. RESULTS Immunohistochemistry detected co-localization of HGF and MET protein in PP. HGF protein levels were significantly higher (P < 0.05) in osteogenic media (day 21: 12.19 ± 8.36 ng/mL) than in E8 medium (day 21: 0.42 ± 0.72 ng/mL). MET inhibitor had a limited feedback effect on the expression profile of the osteogenic genes tested. Gene expression levels for all but three genes were comparable in serum-free and osteogenic media at all time points. CONCLUSION HGF/MET present in human PP and HGF is upregulated in vitro during osteogenesis; however the targeted pathways controlled by MET may not involve osteoblast maturation.

[1]  W. Duncan,et al.  Endocytosed silver nanoparticles degrade in lysosomes to form secondary nanoparticle structures during expression of autophagy genes in osteogenic cells. , 2021, Nanomedicine : nanotechnology, biology, and medicine.

[2]  Noel Ye Naung,et al.  Localization and characterization of human palatal periosteum stem cells in serum‐free, xeno‐free medium for clinical use , 2019, European journal of oral sciences.

[3]  W. Tian,et al.  The establishment of a chemically defined serum-free culture system for human dental pulp stem cells , 2018, Stem cell research & therapy.

[4]  A. Bakopoulou,et al.  Isolation and prolonged expansion of oral mesenchymal stem cells under clinical-grade, GMP-compliant conditions differentially affects “stemness” properties , 2017, Stem Cell Research & Therapy.

[5]  P. Liu,et al.  Targeting MET in cancer therapy , 2017, Chronic diseases and translational medicine.

[6]  M. N. Lee,et al.  Chemical inhibitors of c‐Met receptor tyrosine kinase stimulate osteoblast differentiation and bone regeneration , 2017, European journal of pharmacology.

[7]  A. Herford The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillofacial trauma , 2017, Chinese journal of traumatology = Zhonghua chuang shang za zhi.

[8]  Kevin M. Curtis,et al.  Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair , 2016, Expert opinion on therapeutic targets.

[9]  Rosa Akbarzadeh,et al.  Prospect of Stem Cells in Bone Tissue Engineering: A Review , 2016, Stem cells international.

[10]  C. Marshall,et al.  Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia. , 2015, American journal of human genetics.

[11]  C. Ferretti,et al.  Periosteum derived stem cells for regenerative medicine proposals: Boosting current knowledge. , 2014, World journal of stem cells.

[12]  D. Alexander,et al.  Selection of Osteoprogenitors from the Jaw Periosteum by a Specific Animal-Free Culture Medium , 2013, PloS one.

[13]  R. David,et al.  Human Mesenchymal Stem Cells Display Reduced Expression of CD105 after Culture in Serum-Free Medium , 2013, Stem cells international.

[14]  T. Choueiri,et al.  Targeting the Hepatocyte Growth Factor/c-Met Signaling Pathway in Renal Cell Carcinoma , 2013, Cancer journal.

[15]  W. Luo,et al.  Change in hepatocyte growth factor concentration promote mesenchymal stem cell-mediated osteogenic regeneration , 2012, Journal of cellular and molecular medicine.

[16]  Z. Han,et al.  Safety of Mesenchymal Stem Cells for Clinical Application , 2012, Stem cells international.

[17]  Minqi Li,et al.  A clinical study of alveolar bone tissue engineering with cultured autogenous periosteal cells: coordinated activation of bone formation and resorption. , 2012, Bone.

[18]  B. Liu,et al.  NELL1 promotes bone regeneration in polyethylene particle-induced osteolysis. , 2012, Tissue engineering. Part A.

[19]  Qian Wang,et al.  A Novel Kinase Inhibitor, INCB28060, Blocks c-MET–Dependent Signaling, Neoplastic Activities, and Cross-Talk with EGFR and HER-3 , 2011, Clinical Cancer Research.

[20]  Toshikazu Nakamura,et al.  Hepatocyte growth factor twenty years on: Much more than a growth factor , 2011, Journal of gastroenterology and hepatology.

[21]  S. Mizuno,et al.  The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine , 2010, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[22]  Hwa Sun Kim,et al.  Role of HGF/c-Met in Serum-Starved ARPE-19 Cells , 2007, Korean journal of ophthalmology : KJO.

[23]  G. Christofori,et al.  Hepatocyte growth factor induces cell scattering through MAPK/Egr‐1‐mediated upregulation of Snail , 2006, The EMBO journal.

[24]  G. Karsenty,et al.  ATF4, the Osteoblast Accumulation of Which Is Determined Post-translationally, Can Induce Osteoblast-specific Gene Expression in Non-osteoblastic Cells* , 2004, Journal of Biological Chemistry.

[25]  E. Wagner,et al.  The Fos‐related antigen Fra‐1 is an activator of bone matrix formation , 2004, The EMBO journal.

[26]  Sabine Neuss,et al.  Functional Expression of HGF and HGF Receptor/c‐met in Adult Human Mesenchymal Stem Cells Suggests a Role in Cell Mobilization, Tissue Repair, and Wound Healing , 2004, Stem cells.

[27]  K. Otsuka,et al.  Effects of serum on hepatocyte growth factor secretion and activation by periodontal ligament and gingival fibroblasts. , 2002, Journal of periodontology.

[28]  M. Longaker,et al.  Human NELL‐1 Expressed in Unilateral Coronal Synostosis , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  L. Naldini,et al.  Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth , 1992, The Journal of cell biology.

[30]  A. Bardelli,et al.  Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. , 1991, The EMBO journal.

[31]  S. Zafar,et al.  Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts. , 2020, Journal of oral science.

[32]  Y. Shinonaga,et al.  Alterations in Deciduous Dental Pulp Cells Cultured with Serum-free Medium , 2015 .

[33]  A. Conigrave,et al.  Osteocalcin: An Osteoblast-Derived Polypeptide Hormone that Modulates Whole Body Energy Metabolism , 2014, Calcified Tissue International.

[34]  J. Westendorf,et al.  Regulation of gene expression in osteoblasts , 2010, BioFactors.

[35]  Junwei Yang,et al.  Sp1 and Sp3 transcription factors synergistically regulate HGF receptor gene expression in kidney. , 2003, American journal of physiology. Renal physiology.