Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor‐β1

Abstract

Although mechanical stress as a result of spinal instability is known to cause hypertrophy of the ligameiitum 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-/3 1 (TGF-PI) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamenturn flavum cells (LFCs) were isolated from human ligamenturn flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a cominercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-PI production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, 111, 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-pl antibodies. Production of TGF-PI by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-PI was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-Dl production by LFCs, resulting in hypertrophy of the ligament.

Age-related changes in structure and extracellular matrix protein expression levels in rat tendons

“…The TGF-beta family of growth factors plays an important role in all aspects of tendon function including tendon growth, repair, regulation of mechanically induced collagen synthesis, and ECM turnover (Duncan et al 1999;Nakatani et al 2002). Studies in fibroblasts suggest that CTGF is a down-stream mediator of TGFb1-induced collagen synthesis (Grotendorst et al 1996;Duncan et al 1999).…”

Mechanoregulation of gene expression in fibroblasts

“…In human ligamentum flavum cells subjected to cyclic mechanical stretching, gene expression of collagen types I, III, and V was increased (Nakatani et al, 2002). The increase in collagen mRNA expression due to stretching was markedly reduced by neutralizing endogenous TGF-β1 with anti-TGF-β1 antibody.…”

“…Finally, mechanisms that include triggering autocrine or paracrine release of growth factors such as TGF-β by mechanical loads to regulate the transcription of "mechanoresponsive genes" are also presented (Davies et al, 1997;Sadoshima and Izumo, 1997). Mechanical stress stimulates the release of TGF-β (Lindahl et al, 2002;Nakatani et al, 2002;Yang et al, 2004) as described in the previous section, as well as enhances its gene transcription through activation of EGR-1 . These indirect mechanotransduction mechanisms have been explained in detail previously (Chiquet, 1999;Sarasa-Renedo and Chiquet, 2005).…”

Cyclic stretch enhances apoptosis in human lumbar ligamentum flavum cells via the induction of reactive oxygen species generation

“…Mechanical stretch force could promote transforming growth factor-1 (TGF-β1) production and collagen synthesis by LF cells and result in LF hypertrophy. 7 The apoptosis of ligament cells has been described in previous studies. 8,9 However, the relationship of cyclic stretch and LF cell apoptosis remains largely unknown.…”