Reduced TGF- β Expression and CD206-Positive Resident Macrophages in the Intervertebral Discs of Aged Mice

Biomed Res Int. 2021 Jul 12:2021:7988320. doi: 10.1155/2021/7988320. eCollection 2021.


Age is a key factor in intervertebral disc (IVD) degeneration; however, the changes that occur in IVDs with age are not fully understood. Tissue-resident macrophages are critical for tissue homeostasis and are regulated by transforming growth factor- (TGF-) β. We examined changes in the proportion of resident macrophages in young versus aged mice and the role of TGF-β in regulating resident macrophages in IVDs. IVDs were harvested from 4-month (young) and 18-month-old (aged) C57BL/6J mice. The proportion of macrophages in IVDs was determined using flow cytometry (n = 5 for each time point) and the expression of Cd11b, Cd206, and Tgfb genes, which encode CD11b, CD206, and TGF-β protein, respectively, using real-time PCR. To study the role of TGF-β in the polarization of resident macrophages, resident macrophages isolated from IVDs from young and aged mice were treated with recombinant TGF-β with and without a TGF-β inhibitor (SB431542). Additionally, SB431542 was intraperitoneally injected into young and aged mice, and Cd206 expression was examined using real-time PCR (n = 10 for each time point). The proportion of CD11b+ and CD11b+ CD206+ cells was significantly reduced in aged versus young mice, as was Cd11b, Cd206, and Tgfb expression. TGF-β/IL10 stimulation significantly increased the expression of Cd206, an M2 macrophage marker, in disc macrophages from both young and aged mice. Meanwhile, administration of a TGF-β inhibitor significantly reduced Cd206 expression compared to vehicle control in both groups. Conclusion. Resident macrophages decrease with age in IVDs, which may be associated with the concomitant decrease in TGF-β. Our findings provide new insight into the mechanisms of age-related IVD pathology.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Cells, Cultured
  • Intervertebral Disc / metabolism*
  • Lectins, C-Type / metabolism*
  • Macrophages / metabolism*
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Cell Surface / metabolism*
  • Transforming Growth Factor beta / metabolism*


  • Biomarkers
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Transforming Growth Factor beta