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An In Vitro Organ Culture Model of the Murine Intervertebral Disc
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Macrophage-derived inflammatory cytokines regulate growth factors and pain-related molecules in mice with

Masayuki Miyagi1, Kentaro Uchida1, Shotaro Takano1

  • 1Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa, 252-0374, Japan.

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
|March 7, 2018
PubMed

Insights

Macrophages in injured intervertebral discs (IVDs) produce inflammatory cytokines that upregulate pain-related molecules like growth factors. Macrophage depletion reduces inflammatory cytokines but not growth factors in injured IVDs, revealing complex discogenic pain mechanisms.

Area of Science:

  • Orthopaedic Research
  • Immunology
  • Pain Research

Background:

  • Discogenic low back pain is linked to increased inflammatory cytokines and growth factors.
  • Macrophages are implicated in the inflammatory response within injured intervertebral discs (IVDs).

Purpose of the Study:

  • To investigate macrophage regulation of pain-related molecules in injured IVDs.
  • To determine the role of macrophage-derived molecules in discogenic pain pathogenesis.

Main Methods:

  • Gene expression profiling of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) in intact and injured mouse IVDs.
  • Macrophage depletion using clodronate-laden liposomes to assess its effect on molecule expression.
  • In vitro study of TNF-alpha's effect on F4/80-CD11b-cells from injured IVDs.

Main Results:

  • Injured IVDs showed increased TNF-alpha and IL-1beta, which decreased upon macrophage depletion.
  • NGF and VEGF expression increased in injured IVDs but were unaffected by macrophage depletion.
  • TNF-alpha treatment of macrophages from injured IVDs upregulated NGF, VEGF, cyclooxygenase-2, and mPGES1.

Conclusions:

  • Macrophages in injured IVDs primarily produce inflammatory cytokines, not growth factors.
  • Macrophage-derived inflammatory cytokines play a role in regulating growth factors and pain-related molecules.
  • These findings highlight the intricate mechanisms underlying discogenic pain development.
Keywords:
disc biologyspine

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