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Characterization of joint disease in mucopolysaccharidosis type I mice
Patricia G de Oliveira1, Guilherme Baldo, Fabiana Q Mayer
1Programa de pós-graduação em medicina: ciências medicas, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
Abstract:
Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterized by mutations in enzymes that degrade glycosaminoglycans (GAGs). Joint disease is present in most forms of MPS, including MPS I. This work aimed to describe the joint disease progression in the murine model of MPS I. Normal (wild-type) and MPS I mice were sacrificed at different time points (from 2 to 12 months). The knee joints were collected, and haematoxylin-eosin staining was used to evaluate the articular architecture. Safranin-O and Sirius Red staining was used to analyse the proteoglycan and collagen content. Additionally, we analysed the expression of the matrix-degrading metalloproteinases (MMPs), MMP-2 and MMP-9, using immunohistochemistry. We observed progressive joint alterations from 6 months, including the presence of synovial inflammatory infiltrate, the destruction and thickening of the cartilage extracellular matrix, as well as proteoglycan and collagen depletion. Furthermore, we observed an increase in the expression of MMP-2 and MMP-9, which could conceivably explain the degenerative changes. Our results suggest that the joint disease in MPS I mice may be caused by a degenerative process due to increase in proteases expression, leading to loss of collagen and proteoglycans. These results may guide the development of ancillary therapies for joint disease in MPS I.
Insights
Joint disease in Mucopolysaccharidoses type I (MPS I) involves progressive cartilage degradation. Increased matrix metalloproteinases (MMPs) in MPS I mice contribute to collagen and proteoglycan loss, suggesting a degenerative process.
Area of Science:
- Biochemistry
- Genetics
- Pathology
Background:
- Mucopolysaccharidoses (MPS) are genetic lysosomal storage disorders.
- Joint disease is a common manifestation in MPS, including MPS I.
- Understanding MPS I joint pathology is crucial for therapeutic development.
Purpose of the Study:
- To characterize the progression of joint disease in a murine model of MPS I.
- To investigate the molecular mechanisms underlying joint degeneration in MPS I.
Main Methods:
- Analysis of knee joints from wild-type and MPS I mice at various time points (2-12 months).
- Histological evaluation using Haematoxylin-eosin, Safranin-O, and Sirius Red staining.
- Immunohistochemical analysis of matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9.
Main Results:
- Progressive joint alterations observed from 6 months in MPS I mice.
- Key findings include synovial inflammation, cartilage matrix destruction, and depletion of proteoglycans and collagen.
- Elevated expression of MMP-2 and MMP-9 was noted, correlating with degenerative changes.
Conclusions:
- Joint disease in MPS I mice results from a degenerative process.
- Increased protease expression, particularly MMP-2 and MMP-9, contributes to collagen and proteoglycan loss.
- These findings may inform the development of supportive therapies for MPS I joint complications.
