Bone Abstracts

Introduction: The matrilin-3 polymorphism T298M has been described to be associated with hand osteoarthritis in the carpometacarpal joint 1 (CMC1) and with spinal disc degeneration. In vitro studies revealed that expression levels, processing and secretion of matrilin-3 T298M were similar to the wt protein. Structural analysis indicated an impact on the formation of collagen II/IX/XI heterofibrils, whereas the binding to collagen was not affected. We have now generated a knock in mouse (matrilin-3 T298M/T298M) to investigate the skeletal development and its applicability as a monogenetic model for osteoarthritis.

Methods: The secretion of matrilin-3 in primary chondrocytes was investigated via immunoblot. Micro-CT was used to analyse bone architecture of the forepaw at the age of 4, 8 and 18 weeks. Sequential extraction of newborn femoral head cartilage was performed to assess matrix integrity. Immunostaining was used to investigate the matrix composition in forepaw (newborn, 4, 8, 18 weeks) and spine (newborn, 4 weeks).

Results: Secretion of mutant matrilin-3 by primary chondrocytes was comparable to wt protein and also in tissue there were no signs of intracellular retention. Micro-CT measurements showed no differences in the forepaw. The extractability of the mutant matrilin-3 seems to be increased. The staining of the spine showed an increased collagen IX signal. Analysis of the forepaw by immunohistochemical staining revealed the first evidence of osteoarthritis in the CMC1 joint of matrilin-3T298M/T298M mice at the age of 18 weeks.

Discussion: Previous data suggested that the polymorphism has an impact on fibrillogenesis which might lead to alterations in stability and stiffness of the ECM. The reduced anchorage of matrilin-3 indicated by an increased extractability of the mutant protein might contribute to altered biomechanical properties of the tissue. These alterations in the ECM could be responsible for an early onset of osteoarthritis in transgenetic matrilin three animals.