Collagen type II is downregulated in the degenerative nucleus pulposus and contributes to the degeneration and apoptosis of human nucleus pulposus cells

Mol Med Rep. 2017 Oct;16(4):4730-4736. doi: 10.3892/mmr.2017.7178. Epub 2017 Aug 4.

Abstract

Degenerative disc disease (DDD) is a common degenerative condition initiated mainly within the nucleus pulposus (NP). To date, the etiopathogenesis of DDD remains unclear, and because no effective therapeutic strategies are available to target its pathological processes, DDD is still treated with symptomatic interventions that are far from adequate. Collagen type II is one of the major matrix components of the NP, and is considered to be essential to NP homeostasis. However, the specific mechanisms by which collagen type II influences NP cells remain unknown. In the present study, collagen type II expression was detected using immunohistochemistry analysis and quantitative polymerase chain reaction, and it was demonstrated to be significantly downregulated in NP tissues from patients with DDD compared with nondegenerative controls. To further explore the mechanism in vitro, interleukin (IL)‑1β stimulation was used to induce degeneration of a human NP cell line. IL‑1β stimulation upregulated both the mRNA and protein levels of the catabolic markers matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), while it downregulated the anabolic makers aggrecan and collagen type II. However, addition of purified collagen type II prevented this IL‑1β‑induced metabolic disturbance of the NP cells. Furthermore, IL‑1β stimulation significantly promoted apoptosis in NP cells, while collagen type II treatment decreased the apoptotic rate and the protein levels of cleaved caspase‑3. In conclusion, collagen type II exhibited protective effects in suppressing NP cell degeneration through its anticatabolic, proanabolic and antiapoptotic effects, suggesting that it may be a promising therapeutic agent for the prevention and treatment of DDD.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers
  • Child
  • Collagen Type II / metabolism*
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Intervertebral Disc Degeneration / diagnosis
  • Intervertebral Disc Degeneration / etiology*
  • Intervertebral Disc Degeneration / metabolism*
  • Male
  • Middle Aged
  • Nucleus Pulposus / cytology*
  • Nucleus Pulposus / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Collagen Type II