A July 2019 study 1 examining the pathological effects of cortisol on the intervertebral disc (IVD) cells and human mesenchymal stem cells (hMSCs) of lower back pain (LBP) patients found evidence that stress-and-pain-induced cortisol—especially when chronic—may contribute to IVD degeneration and inhibit the regenerative process of IVD cells.
What’s at Stake?
Chronic LBP is experienced at some point by over 80 percent of the Western population. When caused by disc degeneration, it is often linked to chronic inflammation in the disc and endplates. The pain associated with disc degeneration induces a biochemical stress response that releases the hormone cortisol into the body. This study explored the in vitro effects of stress—and the subsequent release of cortisol—on IVD and stem cells. Specifically, it examined how cortisol might be involved in the degenerative process and in inhibiting cell regeneration in LBP patients.
IVD tissue and bone marrow aspirates (BMA) were collected from six male and female spinal fusion surgery patient donors between the ages of 32 and 54 years old. The cell samples were isolated and cultured before utilizing a 3D microenvironment model consisting of DNA-analyzed, histological pellet sections, light microscopy, and colorizing stain to evaluate the effects of cortisol on their density. Glycosaminoglycan (GAG) analyses quantified how much proteoglycan each sample contained, and paraffin-embedded samples were deparaffinized to find the presence of apoptotic cells. The data retrieved was then analyzed using SPSS 25.0 software.
The results of the data collected in this study indicate that cortisol—especially high amounts—is damaging to cell viability, proliferation, and regeneration. Though hMSC cell viability remained stable seven days after cortisol stimulation, the number of viable cells increased over time, and there was a decrease in hMSC cells treated with cortisol after 14 days when compared to the control group. The cell viability in DC pellets was much lower than the control group 28 days after being treated with cortisol.
A higher number of apoptotic cells also occurred when these glucocorticoid levels were stimulated—a result that agreed with those of previous studies where apoptosis appeared to play a significant role in the loss of viable cells during the progression of IVD degeneration. Previously, very high levels of corticosteroids (including cortisol) were shown to induce apoptosis in certain types of cells, including chondrocytes. The results of the current study suggest stress-induced cortisol imbalance increases IVD degeneration by increasing apoptosis.
DNA content in DC pellets were increased seven days after cortisol treatment but decreased on the 28th day, when treated for both concentrations. The DNA content in hMSC pellets treated with cortisol was lower on day seven and 14 after treatment and dropped even further on day 28.
GAG content in the DC pellets decreased for all groups from day seven, to day 28 after treatment, and the DC pellets had much less GAG on day seven than the control groups. There was a significant reduction in GAG production in the hMSC pellets on day 14 after cortisol treatment, as compared to the control group.
The proteoglycan levels in the hMSC pellets all but disappeared by day 28, though levels had been evident in the DC and hMSC groups on day 14 of the study. The pellet sizes on day 28 were also smaller than the controls of both types of cells, suggesting cell proliferation was inhibited by cortisol. On days seven and 28, more fragmented or apoptotic cells in both the DC and hMSC pellets were detected after being treated with cortisol. Another test found less chondrogenesis than the controls in both pellet groups by days seven and 28.
IVDs receive important nutrients through endplate capillary diffusion. Estrogen receptors have been found in the nucleus propolis of the IVD, which points to the possibility that small hormone proteins like cortisol may reach the IVD through this process. In any event, the stress of chronic LBP could create excessive levels of cortisol in patients, compromising chondrogenic differentiation and the hMSCs’ multipotency.
In this study, chronic cortisol exposure compromised cell proliferation and chondrogenesis in DCs and hMSCs, and excessive levels of stress hormones further jeopardized the ability of the cells to regenerate. The differentiation and immunomodulatory abilities of the in vitro hMSC cells were suppressed by cortisol exposure. The results of this study support the theory that IVD degeneration and regeneration may be negatively affected by pain-induced stress.