title: Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element-binding protein-1 signaling.
abstract: Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (d-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding. Therefore, in this study, glucose was adsorbed to chitosan membranes (CTS-Glc), and the study aimed to investigate whether CTS-Glc complex membranes could regulate the proliferation of human OA chondrocytes and to explore the underlying mechanism. Human OA and SW1353 chondrocytes were used in this study. The experiments involving the transfection of cells used SW1353 chondrocytes. A specific inhibitor and siRNAs were used to investigate the mechanism underlying the CTS-Glc-regulated proliferation of human chondrocytes. We found that CTS-Glc significantly increased the proliferation of both human OA and SW1353 chondrocytes comparable to glucose- or chitosan-only stimulation. The role of mammalian target of rapamycin complex 1 (mTORC1) signaling, including mTOR, raptor, and S6k proteins, has been demonstrated in the regulation of CTS-Glc-increased human chondrocyte proliferation. mTORC1 signaling increased the expression levels of maturated SREBP-1 and FASN and then induced the expressions of cell cycle regulators, that is, cyclin D, cyclin-dependent kinase-4 and -6 in human chondrocytes. This study elucidates the detailed mechanism behind the effect of CTS-Glc complex membranes in promoting chondrocyte proliferation and proposes a possible clinical application of the CTS-Glc complex in the dextrose intraarticular injection of OA prolotherapy in the future to attenuate the pain and discomfort of OA patients.
authors.affiliation: Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Chang
authors.affiliation: Department of Orthopaedics, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Chin-Chang
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedics and Traumatology, Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Su
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
authors.forename: Ko-Chao
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
authors.forename: Hsin-I
authors.identifier: http://orcid.org/0000-0002-1278-6958
authors.initials: HI
authors.lastname: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000327:Adsorption; D000368:Aged; D018501:Antirheumatic Agents / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008567:Membranes, Artificial; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D000076242:mTOR Associated Protein, LST8 Homolog
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018501:Antirheumatic Agents; C530104:CCND1 protein, human; C555285:MLST8 protein, human; D008567:Membranes, Artificial; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D000076242:mTOR Associated Protein, LST8 Homolog; D019938:Cyclin D1; D048271:Chitosan; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D005947:Glucose
keywords: SREBP-1; chitosan; chondrocyte; glucose; proliferation