Biological Approaches to Spinal Disc Repair and Regeneration for Clinicians by Roger Hartl Larry Bonassar

Author:Roger Hartl,Larry Bonassar
Language: eng
Format: epub
Publisher: Thieme Medical Publishing Inc.
Published: 2017-05-10T00:00:00+00:00

12.1 Introduction

Degenerative disc diseases (DDDs) consist of various pathologies, such as intervertebral disc (IVD) herniation and discogenic low back pain, which cause various clinical symptoms. Generally, degenerated discs are characterized clinically by a reduction of disc height or IVD herniation as demonstrated by magnetic resonance imaging (MRI) or computed tomography (CT). These changes are considered to be caused by an imbalance of anabolism and catabolism, or homeostasis, of the disc cells residing in the nucleus pulposus (NP) and annulus fibrosus (AF).1 The modulation of disc cell metabolism involves a variety of molecules, including cytokines, enzymes, enzyme inhibitors, and growth factors.2 Although the pathogenesis of DDD is not yet fully understood, DDDs are characterized by a progressive process involving a combination of several factors, such as genetic background, aging, and mechanical stress. These changes result in the reduction of water content associated with the depletion of proteoglycans in the NP and structural changes or fissures in the AF. Genetic studies have shown relationships between DDDs and polymorphisms3 in genes encoding collagen type I,4 collagen type X,5,6 aggrecan,7 matrix metalloprotease-2 (MMP-2),8 MMP-3,9 interleukin-1 α (IL-1 α),10 IL-6,11 asporin,12 and cartilage intermediate layer protein, otherwise known as CILP.13,14

Considering these characteristics, to treat DDDs, many efforts have investigated therapeutic strategies that stimulate matrix synthesis by growth factors or inhibit inflammatory cytokines, such as IL-1 and tumor necrosis factor- α (TNF- α).15,16,17 Some efforts have developed therapeutic approaches to suppress disc degeneration by regulating the effects of proteolytic enzymes, such as MMP-1, MMP-3, and members of the disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS) family.18,19,20 However, if treatment is aimed at recovering disc structure damage, the direct stimulation of cells contributing to matrix metabolism may be required. Since the pioneering work by Thompson et al,21 the effects of a variety of growth factors have been tested (see reviews3,22,23) and have been shown to include an inhibitory effect on matrix degradation or cytokine expression.3,24,25

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