Ritva Inkinen

Proteoglycans and Hyaluronan in the intervertebral Disc and Cartilage

Endplate -­ Effects of Aging and Degeneration

Opponent

Professor Bruce Caterson, University of Cardiff, United Kingdom

Reviewers

Docet Sally Roberts, Robert Jones and Agnes Hunt Orthopaedic Hospital, United Kingdom

Associate professor Mats Grönblad, University Hospital of Helsinki, Finland

Supervisors

Professor Markku Tammi, University of Kuopio, Finland

Docent Mikko Lammi, University of Kuopio, Finland

Docent Kaija Puustjärvi, University Hospital of Helsinki, Finland

Articles of the thesis

Spinal disorders form one of the most common disability in the middle-aged population of the western countries.Spinal disorders are an expanding health problem and althoughthe economic impact on society is vast, the pathophysiology of the spinal disorders still has not been clarified in detail.

   Proteoglycans (PGs) and hyaluronan (HA) are essential macromolecules for the function of the intervertebral disc and cartilage endplates. They also reflect tissue changes  during aging and degeneration. PGs and HAZ were investigated in this study to find specific age- and degeneration related alterations in the human, canine and porcine intervertebral disc and cartilage endplate. In addition, the effects of two widely used anti-inflammatory drugs (NSAIDs), tiaprofenic acid and indomethacin, were studied in an experimental porcine disc degeneration model.

   In the human intervertebral disc, the content of small PGs increased, and the glycosylation of large PGs was altered with disc degeneration, while less change was associated with aging. The alterations in PG content and glycosylation in degeneration differed from those in aging or maturation.

   In animal experimental model, degenerative changes were seen mainly in the nucleus pulposus, although the process was induced by a scalpel wound in the annulus fibrosus. An injury in the annulus fibrosus alters the biomechanics, nutrition and metabolism of the cells and changes matrix production and degradation. The PG alterations in a degenerating porcine disc were modified by administration of the NSAIDs. Tiaprofenic acid may afford protection to the PGs, at least during the early phases after disc injury.

   Most HA was found in the inner parts of the disc. Particularly in human discs, cell-associated HA appeared to be masked, probably by aggrecan, whereas there was less masking of HA in the interterritorial matrix. In the canine cartilage endplate, HA was clearly cell-associated, even appearing inside the chondrocytes. Whether this is a sign of synthesis or uptake and degradation of HA remains unclear. In the outer annulus fibrosus, HA was located between the collagenous lamellae, perhaps serving as lubricant when the lamellae slide along each other.

   This study confirms the biochemical and biomechanical importance of PGs and HA in the extracellular  matrix of spinal tissues. Large PGs and HA were more concentrated in the inner parts of the disc. The changes in in large PG glycosylation and small PG concentration in degeneration is suggested to reflect an alteration in cellular differentiation, or to result from cleavage by proteinases, leading to inappropriate structures for the biomechanical environment of the disc. The animal moidels give valuable information about the normal structure and pathogenesis of the intervertebral disc and cartilage endplate. The more we know about the normal function of the disc, the more possibilities there are for more specific treatments of spinal diseases.

  1. Kääpä E, Holm S, Inkinen R, Lammi MJ, Tammi M, Vanharanta H: Proteoglycan chemistry in experimentally injured intervertebral disk. J Spinal Disord 7:296-306, 1994

  2. Karppinen J, Inkinen RI, Kääpä E, Lammi MJ, Tammi MI, Holm S, Vanharanta H: Effects of tiaprofenic acid and indomethacin on proteoglycans in the degenerating porcine intervertebral disc. Spine 20: 1170-1177, 1995

  3. Inkinen RI, Lammi MJ, Lehmonen S, Puustjärvi K, Kääpä E, Tammi MI: Relative increase of biglycan and decorin and altered chondroitin sulfate epitopes in the degenerating human intervertebral disc. J Rheumat 25: 506-514, 1998

  4. Inkinen RI, Lammi MJ, Ågren U, Tammi R, Puustjärvi K, Tammi MI: Hyaluronan distribution in the human and canine intervertebral disc and cartilage endplate. Histochem J 31: 579-588, 1999

Related articles

  1. Puustjärvi K, Lammi M, Helminen H, Inkinen R, Tammi M: Proteoglycans in the intervertebral disc of young dogs following strenous running exercise. Connect Tissue Res 30: 225-240, 1994

  2. Lammi P, Inkinen RI, von der Mark K, Puustjärvi K, Arokoski J, Hyttinen MM, Lammi MJ: Localization of type X collagen in the intervertebral disc of mature beagle dogs. Matrix Biol 17: 449-453, 1998

  3. Sahlman J, Inkinen R, Hirvonen T, Lammi MJ, Lammi PE, Nieminen J, Lapveteläinen T, Prockop DJ, Arita M, Li SW, Hyttinen MM, Helminen HJ, Puustjärvi K: Premature vertebral endplate ossification and mild dics degeneration in mice after inactivation of one allele of the Col2a1 gene for type II collagen. Spine 26: 2558-2565, 2001

Last updated January 29, 2019