Receptor activator of nuclear factor kappa B ligand in an experimental intervertebral disc degeneration

This study was designed to clarify the role of the receptor activator of nuclear factor kappa B ligand (RANKL) in the process of discus degeneration and spondylarthrosis. It was hypothesized that experimental discus lesion would initiate not only local bone remodelling but also increased osteoclast formation on a location remote to the injury site due to altered spinal biomechanics. It was speculated that these changes in vertebral bone remodelling could be reflected in an increased RANKL expression.

The presence of RANKL in the spine was studied in an experimental perforating lesion of the cranial endplate of L4 and the adjoining disc in six domestic pigs and in one human herniated disc. After three months, the experimental and contiguous control vertebrae, complete with intervertebral discs, were subjected for immunohistochemistry.

This is the first study to show that RANKL was locally seen (produced) in osteoblasts, fibroblasts replacing annulocytes and mesenchymal bone marrow cells and, in part, apparently bound to the surface of osteoclasts and macrophage-like prefusion macrophages. Such RANKL induction was also seen at sites remote from the experimental lesion driving the whole process. More RANKL-positive cells were found in close proximity to the endplate than in the central parts of the vertebrae. Osteocytes in bone matrix and most bone marrow cells in the marrow microenvironment showed no RANKL staining. Human annulus fibrosus also contained RANKL, RANK and OPG.

We have demonstrated that RANKL is produced locally, also in soluble form, at the site of injury and also in intact vertebrae and bony structures likely due to altered biomechanics. It seems to be engaged in bone healing and remodelling, essentially proving our working hypothesis. These secondary bone changes could represent part of the degenerative spine disease (spondylarthrosis). RANKL inhibitors, like recombinant human osteoprotegerin (OPG), could be interesting drugs to test, not only in osteoporosis, but also in spondylarthrosis.