Morphology and TGF-beta1 Concentration Analysis of Ligamentum Flavum in Patients with Lumbar Canal Stenosis and Lumbar Disc Herniation

Abstract

The most common spinal disorder in elderly patients is lumbar spinal canal stenosis, causing low back and leg pain and paresis. The aetiology of degenerative changes occurring in lumbar stenosis remain unclear: some authors hypothesize hyperplasia and others hypertrophy of the LF. The change in LF is known to be related to degenerative changes secondary to the aging process or mechanical instability. This study aimed to analyse the ligamentum flavum (LF) of patients with lumbar canal stenosis and lumbar disc herniation to evaluate the morphology and concentration of the Transforming Growth Factor-beta 1 (TGF-beta 1). The study was undertaken in three phases: A) Measurement of the thickness of the ligamentum flavum in patients with lumbar stenosis and/or herniated lumbar disc through axial T1 weighted lumbo-sacral MR images; B) Removal of ligamentum flavum in patients undergoing intervention for lumbar stenosis and lumbar disc herniation (control group); C) Optical microscopy study of the morphology of degenerated ligamentum and immunohistochemical analysis to assess the concentration of TGF-beta 1 in the LF. Morphological analysis of the LF (i.e. the increase in the number of fibres or distension and relaxation of the same as a result of degenerative processes) and the presence or absence of a high concentration of TGF-beta1 (then more fibroblasts involved in the degenerative process) can be important to establish whether there is hypertrophy or hyperplasia of the LF in lumbar canal stenosis. The current study showed that decreased elasticity of the LF in the elderly is due to a loss of elastic fibres that are degenerated and a concomitant increase in collagenous fibres (hypertrophy). TGF-beta1 concentrations of the LF were higher in lumbar spinal stenosis than in disc herniations. This suggest that LF of lumbar canal stenosis is hypertrophic: LF hypertrophy could be due to thickening of the normal elastic layer and the abnormal collagenous layer and to higher expression of TGF-beta 1 by fibroblasts.

Keywords

ligamentum flavum transforming growth factor beta 1 hypertrophy hyperplasia lumbar canal stenosis

Get full access to this article

View all access options for this article.

References

Kosaka

Sairyo

Biyani

: Pathomechanism of loss of elasticity and hypertrophy of lumbar ligamentum flavum in elderly patients with lumbar spinal canal stenosis. Spine 32(25): 2804–2811, 2007.

Nakatani

Marui

Hitora

: Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor-beta 1. J Orthop Res 20(6): 1380–1386, 2002.

Massagué

: The transforming growth factor-beta family. Annu Rev Cell Biol 6: 597–641, 1990.

Miyazono

Heldin

: The mechanism of action of transforming of growth factor beta. Gastroenterol Jpn 28 (suppl): 81–85, 1993.

Roberts

: Molecular cell biology of TGF-beta 1. Miner Electrolyte Metab 24: 111–119, 1998.

Rauschning

: Normal and pathologic anatomy of the lumbar root canal. Spine 12: 1008–1019, 1987.

Yong-Hing

Reilly

Kirkaldy-Willis

: The ligamentum flavum. Spine 1: 226–234, 1976.

Zarzur

: Anatomic studies of the human ligamentum flavum. Anesth Analg 3: 499–502, 1984.

Ramsey

: The anatomy of the ligamenta flava. Clin Orthop 44: 129–140, 1996.

10.

Sairyo

Biyani

Goel

: Pathomechanism of ligamentum flavum hypertrophy: A multidisciplinary investigation based on clinical, biomechanical, histologic, and biologic assessments. Spine 30(23): 2649–2656, 2005.

11.

Fukuyama

Nakamura

Ikeda

: The effect of mechanical stress on hypertrophy of the lumbar ligamentum flavum. J Spinal Disord 8: 126–130, 1995.

12.

Yoshida

Shima

Tangiguti

: Hypertrophied ligamentum flavum in lumbar spinal canal stenosis: Pathogenesis and morphologic and immunohistochemical observation. Spine 17: 1353–1360, 1992.

13.

Specchia

Pagnotta

Gigante

: Characterization of cultured human ligamentum flavum cells in lumbar spine stenosis. J Orthop Res 19(2): 294–300, 2001.

14.

Schräder

Grob

Rahn

: Histology of the ligamentum flavum in patients with degenerative lumbar spinal stenosis. Eur Spine 18 (4): 323–328, 1999.

15.

Inaba

Matsunaga

Ishidou

: Effect of transforming growth factor beta 1 on fibroblasts in ossification of the posterior longitudinal ligament. In Vivo 10: 445–449, 1996.

16.

Kawaguchi

Kurokawa

Hoshino

: Immunohistochemical demonstration of bone morphogenic protein-2 and transforming growth factor beta 1 in the ossification of the posterior longitudinal ligament of the cervical spine. Spine 17(suppl): 33–36, 1992.

17.

Zhong

Chen

: Overexpression of transforming growth factor-beta 1 in degenerative ligamentum flavum. ] nan Fang Yi Ke Da Xue Xue Bao. 29 (2): 216–218, 2009.