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

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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-β1 (TGF-β1) 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-β1 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-β1 antibodies. Production of TGF-β1 by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-β1 was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-β1 production by LFCs, resulting in hypertrophy of the ligament. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.