title: Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor-beta1.
abstract: Although mechanical stress as a result of spinal instability is known to cause hypertrophy of the ligamentum flavum resulting in degenerative spinal canal stenosis, the mechanism of the ligament hypertrophy is not well understood. In the present study, we investigated the effect of mechanical stretching force on collagen synthesis and transforming growth factor-beta1 (TGF-beta1) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamentum flavum cells (LFCs) were isolated from human ligamentum flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a commercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-beta1 production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, III, and V in LFCs subjected to mechanical stretching force. The increase in collagen gene expression of LFCs was inhibited in the presence of anti-TGF-beta1 antibodies. Production of TGF-beta1 by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-beta1 was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-beta1 production by LFCs, resulting in hypertrophy of the ligament.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University School of Medicine, 7-5-1 Kusunoki-cho Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Marui
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hitora
authors.forename: Minoru
authors.initials: M
authors.lastname: Doita
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017843:Ligamentum Flavum / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D000906:Antibodies; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen