Can heat shock proteins protect disc cells against death?

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Sally Roberts, Robert Jones and Agnes Hunt Orthopaedic Hospital and ISTM, Keele University, UK, presented the the results of the paper “Disc cell clusters in pathological human intervertebral disc are associated with increased stress protein immunostaining” Eurospine Congress in Vienna, Austria.

“IVD cells within the annulus fibrosus (AF) and nucleus pulposus (NP) maintain distinct functional extracellular matrices and operate within a potentially noxious and stressful environment,” the authors wrote as background information. “How disc cells respond to stress and whether stress is responsible for triggering disc degeneration is unknown.  Disc cell proliferation and cluster formation are most marked in degenerate IVDs, possibly indicating attempts at matrix repair. In other tissues, stress proteins increase rapidly after stress protecting cell function and, although implicated in degeneration of articular cartilage, have received little attention in degenerative IVD pathologies.”

 

Stress proteins, Roberts said, are more commonly known as heat shock proteins (Hsps). “Hsps are molecular chaperones, and aid in the folding and maintenance of newly translated proteins and can also lead to the degradation of misfolded and destabilised proteins,” she said.

 

The aim of this study, Roberts told delegates, was to determine if Hsp27 and Hsp72 and the heat shock factor 1 (HSF-1) were present in pathological human discs. The investigators compared the distribution of stress protein immunolocalisation in pathological and control IVDs. Samples of 59 discs were obtained from 43 patients with herniation (mean age 42+/-14 years) and degenerative disc disease (DDD) (mean age 45+/-11 years) at surgery and 12 controls at postmortem (mean age 62+/-18 years).

 

Tissues were immunostained with a polyclonal antibody for HSF-1 and monoclonal antibodies for the Hsps 27 and 72, using an indirect immunoperoxidase method. Positively stained cells were expressed as a percentage of the total. Cell cluster formation was also assessed.

 

The proportion of cells in clusters was similar in AF (both 2%) and NP (8 and 9%) of control and DDD samples, whereas in herniated tissues this was increased (AF 12%, NP 14%). Stress antigen staining tended to be more frequent in clustered rather than in single/doublet cells, and this was significant (p<0.005) in both the AF and NP of herniated discs.

 

In conclusion, Roberts said, Hsps 27 and 72 and HSF-1 were present in surgical disc samples, more Hsps were present in cells in clusters and more cells in herniated discs were in clusters. “We know that cells in the disc can die via different pathways, either by the less destructive route of apoptosis or alternatively the more damaging necrosis. We know that heat shock proteins interact and interfere with those pathways and appear to be able to protect the cells against cell death and/or and other processes such as cellular senescence.”

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