title: Isolation of mesenchymal stem cells from human ligamentum flavum: implicating etiology of ligamentum flavum hypertrophy.
abstract: METHODS
  To demonstrate the existence of mesenchymal stem cells (MSCs) in ligamentum flavum (LF) and their pathogenic role in LF hypertrophy.
  
  
  OBJECTIVE
  To isolate and characterize LF-derived MSCs and their response to transforming growth factor-beta 1 (TGF-β1) and trichostatin A (TSA), a histone deacetylase inhibitor (HDACi).
  
  
  BACKGROUND
  LF is a connective tissue, of which hypertrophic changes induce spinal stenosis. The pathogenic role of TGF-β1 in spinal stenosis has been implicated. TSA has been shown to suppress TGF-β1-induced alpha-smooth muscle actin (α-SMA), type I and III collagen synthesis in a variety of cells. MSCs have been isolated from a variety of adult tissues, except LF. Whether MSCs exist in LF and their response to TGF-β1 and TSA is not clear.
  
  
  METHODS
  The MSCs from LF were isolated and cultured. Their phenotypic character, linage differentiation potential, and response to TGF-β1 and TSA were analyzed.
  
  
  RESULTS
  LF-derived MSCs have the similar profile of surface markers as bone marrow MSCs. They were demonstrated to have the potential to be differentiated into osteoblasts, adipocytes, and chondrocytes. Administration of TGF-β1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and increased the gene expression and protein level of α-SMA. TSA blocked the fibrogenic effects of TGF-β1.
  
  
  CONCLUSIONS
  The current results demonstrated the isolation of MSCs from LF. The cellular response to TGF-β1 implied that these cells might play an important role in the pathogenesis of LF hypertrophy. TSA, which blocks the effects of TGF-β1, may be a potent therapeutic choice for inhibiting LF hypertrophy.
authors.affiliation: Department of Orthopedics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Te
authors.initials: YT
authors.lastname: Chen
authors.forename: Jyh-Ding
authors.initials: JD
authors.lastname: Wei
authors.forename: Jung-Pan
authors.initials: JP
authors.lastname: Wang
authors.forename: Hsieh-Hsing
authors.initials: HH
authors.lastname: Lee
authors.forename: En-Rung
authors.initials: ER
authors.lastname: Chiang
authors.forename: Hung-Chang
authors.initials: HC
authors.lastname: Lai
authors.forename: Ling-Lan
authors.initials: LL
authors.lastname: Chen
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Lee
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Tsai
authors.forename: Chien-Lin
authors.initials: CL
authors.lastname: Liu
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D006984:Hypertrophy; D007150:Immunohistochemistry; D017843:Ligamentum Flavum / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009130:Muscle, Smooth / Q000737:chemistry; D010006:Osteoblasts / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000199:Actins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D053773:Transforming Growth Factor beta1; D053495:Osteopontin; C012589:trichostatin A; D003094:Collagen