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

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-) . We examined changes in the proportion of resident macrophages in young versus aged mice and the role of TGF- 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 ( = 5 for each time point) and the expression of , , and genes, which encode CD11b, CD206, and TGF- protein, respectively, using real-time PCR. To study the role of TGF- in the polarization of resident macrophages, resident macrophages isolated from IVDs from young and aged mice were treated with recombinant TGF- with and without a TGF- inhibitor (SB431542). Additionally, SB431542 was intraperitoneally injected into young and aged mice, and expression was examined using real-time PCR ( = 10 for each time point). The proportion of CD11b+ and CD11b+ CD206+ cells was significantly reduced in aged versus young mice, as was , , and expression. TGF-/IL10 stimulation significantly increased the expression of , an M2 macrophage marker, in disc macrophages from both young and aged mice. Meanwhile, administration of a TGF- inhibitor significantly reduced expression compared to vehicle control in both groups. . Resident macrophages decrease with age in IVDs, which may be associated with the concomitant decrease in TGF-. Our findings provide new insight into the mechanisms of age-related IVD pathology.