Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

Abstract

Background Intervertebral disc degeneration is a common condition with few inexpensive and effective modes of treatment, but current investigations seek to clarify the underlying process and offer new treatment options. It will be important for physicians to understand the molecular basis for the pathology and how it translates to developing clinical treatments for disc degeneration. In this review, we sought to summarize for clinicians what is known about the molecular processes that causes disc degeneration.

FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration

“…Four‐month‐old skeletally mature AcanCreER −/− ; Foxo1 fl/fl ; Foxo3 fl/fl ; and Foxo4 fl/fl (AcanCreER −/− ) and AcanCreER +/− ; Foxo1 fl/fl ; Foxo3 fl/fl ; and Foxo4 fl/fl (AcanCreER‐FOXO KO) mice were injected with tamoxifen, and FOXO expression was assessed 2 weeks later by qPCR analysis (Supporting information Figure S5 in Appendix S1). Unlike the results in the Col2a1‐Cre model, the reduction in FOXO expression upon tamoxifen administration in the AcanCreER model was more marked in the NP than in the AF, consistent with higher aggrecan expression in NP than in AF (Anderson & Tannoury, 2005; Boos et al, 2002; Kadow et al, 2015). Histopathological analysis revealed no differences in cellularity or disk height between genotypes at 6 months of age (Figure 3a–c).…”

“…Loss of NP cellularity is one of the earliest and most important events in IDD that is hypothesized to drive the progression of the disease (Anderson & Tannoury, 2005; Ding, Shao, & Xiong, 2013; Kadow et al, 2015; Vergroesen et al, 2015). NP cells are unique in their ability to adapt to their physiological environment, defined by low‐oxygen and nutrient levels (Bartels, Fairbank, Winlove, & Urban, 1998).…”

“…The principal underlying causes of IDD are changes in cell numbers and phenotype and compromised biomechanical function in the IVD (Deyo & Weinstein, 2001). Aging is the major risk factor for IDD (Miller, Schmatz, & Schultz, 1988), and previous studies achieved substantial progress in describing age‐related changes in all IVD tissues, namely nucleus pulposus (NP), annulus fibrosus (AF), and endplates (EP) (Anderson & Tannoury, 2005; Boos et al, 2002; Kadow, Sowa, Vo, & Kang, 2015). Unlike any other connective tissues, age‐related changes in the IVD start early in life and involve a reduction in viable cells, particularly in the NP, and changes at the cellular and molecular level result in structural and functional impairment of the ECM, eventually leading to biomechanical failure and degeneration (Anderson & Tannoury, 2005; Kepler, Ponnappan, Tannoury, Risbud, & Anderson, 2013; Sivan, Wachtel, & Roughley, 2014; Vergroesen et al, 2015).…”

Lumbar Disc Herniation

“…The central NP is a site of collagen secretion and contains numerous proteoglycans (PG), which facilitate water retention, creating hydrostatic pressure to resist axial compression of the spine [3,4]. The NP is primarily composed of type II collagen, which accounts for 20% of its overall dry weight.…”

The Relationship between Lifestyle and Pain in Patients with Spinal Disc Herniation

“…Nevertheless, osteoarthritis involves degenerative damages, occurring to the disc that causes upper and lower vertebrae reactions of bone and disc growth, which in turn can lead to pressure to inside of the channel (Kadow ., 2015). In the lifestyle of people in which nutrition, exercise, stress management, optimism and interpersonal relationships are involved are altogether directly affect the level of pain (Chaman , 2015).…”