Characterization of Joint Disease in Mucopolysaccharidosis Type I Mice and the Effects of Enzyme Replacement Therapy

Patricia Oliveira¹, Guilherme Baldo², Fabiana Mayer², Barbara Martinelli², Luise Meurer³, Roberto Giugliani², Ursula Matte² and Ricardo M. Xavier⁴, ¹Rheumatology, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil, ²Genetics, Hospital de Clinicas de Porto Alegre, ³Pathology, Hospital de Clinicas de Porto Alegre, ⁴Rheumatology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: joint destruction, matrix metalloproteinase (MMP) and osteoarthritis

Session Information

Title: Miscellaneous Rheumatic and Inflammatory Diseases: Periodic Fever Syndromes

Session Type: Abstract Submissions (ACR)

Background/Purpose: Mucopolysaccharidosis type I (MPS I) is a lysosomal disorder caused by deficiency of alpha-L-iduronidase, which leads to storage of glycosaminoglycans. Patients with MPS I present destructive changes in their joints in a process not well understood. The MPS I animal model is a useful tool to study the disease pathogenesis; however the changes in the MPS I joints were never investigated. This work aimed to describe the joint disease progression in the murine model of MPS I, and the effect of treatment with enzyme replacement therapy (ERT).

Methods: Normal (wild type) and untreated MPS I mice were sacrificed at different time points (from 2 to 12 months). In addition, some MPS I mice were treated with ERT and sacrificed at 6 months. The knee joints were collected and hematoxylin and eosin staining was used to evaluate the articular architecture. Safranin-O and Sirius-Red staining was used to analyze proteoglycans (PGs) and collagen content. In addition we analyzed the expression of matrix-degrading metalloproteinases (MMPs), MMP-2 and -9, by immunohistochemistry.

Results: We observed progressive joint alterations from 6 months, including presence of synovial inflammatory infiltrate, destruction and thickening of the cartilage extracellular matrix and PGs and collagen depletion. Also, we observed an increase in the expression of MMP-2 and -9, which could explain the degenerative changes. We also investigated the effect of ERT when started at 2 months, which showed no benefits, suggesting that the poorly vascularized cartilage is difficult to reach, and an ancillary therapy might be needed for patients.

Conclusion: Our results suggest that the degenerative joint and bone disease in MPS I animals presents some similarities to osteoarthritis. More important, our results evidence the need for and an ancillary therapy for patients.

Disclosure:

P. Oliveira,
None;

G. Baldo,
None;

F. Mayer,
None;

B. Martinelli,
None;

L. Meurer,
None;

R. Giugliani,
None;

U. Matte,
None;

R. M. Xavier,
None.

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