Bone and Joint Diseases

 Dr. Yoshiyuka Yasuda, Dr. Susan Wilson, Saadat Hashamiyan

Osteoporosis and various forms of arthritis are disabling bone and joint diseases predominantly afflicting the elderly population.  Post-menopausal and senile osteoporosis lead to a progressive bone loss resulting in an increase of bone fractures.  Osteo- and rheumatoid arthritis cause an irreversible loss of articular cartilage accompanied with a loss of function of the affected joints. Cathepsins such as cathepsin K have been demonstrated to be critical in osteoclast-mediated bone resorption and cartilage erosion.  In addition, cathepsin S may play a crucial role in the inflammatory component of arthritis.   

  To investigate the role of cathepsins in bone and cartilage diseases, we exploit a rheumatoid arthritis model (DBA 1 mice) and a lysosomal storage disease model (MPS1) which displays massive bone deformations. Cathepsin-deficient mice are used to explore the role of individual cathepsins in those diseases. Reduction of bone and cartilage loss in cathepsin K-deficient DBA 1 mice was demonstrated (rheumatoid arthritis model)

 

 

 

 

 

Immuno-histochemical staining of cathepsin K (a) and heparan sulfate (HS) (b) in shoulder joint of mice. HS is overproduced in MPS1 and it has been shown to inhibit cathepsin K. Our hypothesis is that HS inhibits cathepsin K in MPS1 and thus leads to aberrations in bone remodeling and subsequently to bone deformations.