首页|FKBP5 Regulates the Osteogenesis of Human Adipose-derived Mesenchymal Stem Cells

FKBP5 Regulates the Osteogenesis of Human Adipose-derived Mesenchymal Stem Cells

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Objective:Human adipose-derived stem cells(ASCs)have shown considerable potential for tissue regeneration.FK506 binding protein(FKBP)5 is a cochaperone of several proteins.The purpose of this work was to explore the function of FKBP5 in ASC osteogenesis.Methods:Lentivirus infection was used to overexpress or knock down FKBP5 in ASCs.To inhibit FKBP5,SAFit2,a specific inhibitor of FKBP5,was used.Next,the osteogenic capacity of ASCs was evaluated via alkaline phosphatase(ALP)staining,and extracellular calcium precipitation was detected via Alizarin red S staining.The binding proteins of FKBP5 were assessed via proteomics and validated via coimmunoprecipitation experiments.Results:Following osteogenic induction,FKBP5 expression increased at both the mRNA and protein levels.Interestingly,FKBP5 upregulation by lentivirus infection increased the ability of ASCs to differentiate into osteoblasts,as revealed by ALP staining,while ALP activity also increased.Moreover,increased extracellular calcium precipitation confirmed that FKBP5 overexpression promoted ASC osteogenesis into osteocytes.On the other hand,FKBP5 knockdown or functional suppression with SAFit2 decreased this process.Furthermore,the proteomics and coimmunoprecipitation data demonstrated that FKBP5 bound to a variety of proteins in ASCs.These proteins serve as the molecular chaperone base upon which the osteogenesis-regulating activity of FKBP5 rests.Conclusion:Our study revealed that FKBP5 enhances the osteogenesis of ASCs,providing a feasible method for clinical bone tissue engineering applications.

human adipose-derived mesenchymal stem cellsFK506 binding protein 5osteogenic differentiationco-chaperonebone tissue engineering

Xiao-yu TIAN、Biao ZHU、Wen-can FANG、Xiang-bin ZHOU、Ning WU、Hong LI、Ning WEN、Jin LI

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Department of Stomatology,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China

Beijing Key Laboratory of Neuropsychopharmacology,State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China

Medical School of Chinese PLA,Beijing 100853,China

Department of Stomatology,Fuxing Hospital,Capital Medical University,Beijing 100038,China

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2024

10.1007/s11596-024-2941-8

当代医学科学(英文)
华中科技大学同济医学院

当代医学科学(英文)

影响因子：0.748
ISSN：2096-5230
年,卷(期)：2024.44(6)