Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair

Abstract

A growing body of evidence in humans and animal models indicates an association between intervertebral disc degeneration (IDD) and increased fibrotic elements in the nucleus pulposus (NP). These include enhanced matrix turnover along with the abnormal deposition of collagens and other fibrous matrices, the emergence of fibrosis effector cells, such as macrophages and active fibroblasts, and the upregulation of the fibroinflammatory factors TGF-β1 and IL-1/-13. Studies have suggested a role for NP cells in fibroblastic differentiation through the TGF-βR1-Smad2/3 pathway, inflammatory activation and mechanosensing machineries. Moreover, NP fibrosis is linked to abnormal MMP activity, consistent with the role of matrix proteases in regulating tissue fibrosis. MMP-2 and MMP-12 are the two main profibrogenic markers of myofibroblastic NP cells. This review revisits studies in the literature relevant to NP fibrosis in an attempt to stratify its biochemical features and the molecular identity of fibroblastic cells in the context of IDD. Given the role of fibrosis in tissue healing and diseases, the perspective may provide new insights into the pathomechanism of IDD and its management.

Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects

“…To treat IVDD fundamentally, rather than to relieve symptoms, treatments focusing on IVDD-related pathogenesis are the emerging trends in the field. Pathogenic mechanisms, such as inflammation, autophagy, and fibrosis, may act as potential therapeutic targets for IVDD [ 24 , 41 ]. As an effective strategy to prevent and treat IVDD pathogenesis, this study is the first to report that PA not only reduces inflammation and fibrosis, but also promotes autophagy, thereby improving IVDD progression.…”

“…Responsive to the stimulation of TGF-β1, NP cell fibrosis progression not only up-regulates fibrotic protein [α-smooth muscle actin (α-SMA) and type I collagen (Col1a1)] expression, leading to NP sclerosis and loss of elasticity, but also further promotes inflammation and accelerates IVDD deterioration [ 22 ]. Therefore, to break this vicious cycle, anti-inflammatory [ 23 ] and anti-fibrosis strategies [ 24 ] are pivotal during IVDD progression [ 23 ]. Thus, exploring new drugs to treat IVDD is imperative.…”

An Injectable Hydrogel Scaffold Loaded with Dual-Drug/Sustained-Release PLGA Microspheres for the Regulation of Macrophage Polarization in the Treatment of Intervertebral Disc Degeneration

“…TNF-α can be used to induce intervertebral disc degeneration [48]. The degeneration of nucleus pulposus cells was induced by TNF-α 50 ng/mL for 6 h. The extracellular matrix of degenerative nucleus pulposus cells showed a reduction in proteoglycans and type II collagen and an increase in matrix metalloproteinase MMP13 [49]. The RNA expression of aggrecan, collagen II, and MMP13 in nucleus pulposus cells was detected by q-PCR (Figure 5B-D).…”

Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration

“…The dynamic balance of ECM composition and content determines the structural and functional integrity of the NP (Xin et al, 2022). ECM catabolic enzymes show high expression in degenerating NP cells, such as matrix metalloproteinases (MMPs) and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS), ultimately leading to ECM degradation (Nagase and Kashiwagi, 2003;Wang et al, 2015;Sun et al, 2022). Therefore, we should pay attention to the dynamic balance of ECM anabolism and catabolism, which is the key to the treatment of IVDD.…”