Proteomics

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Proteomic Screening Identifies Novel Biomarkers and Mechanisms of Synovial Joint Disease in a Canine Model of Mucopolysaccharidosis I


ABSTRACT: Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this study was to leverage the naturally-occurring MPS I canine model and undertake an unbiased proteomic screen to identify systemic biomarkers predictive of local joint disease in MPS I. Synovial fluid and serum samples were collected from MPS I and healthy dogs at 12 months-of-age, and protein abundance characterized using LC MS/MS. Stifle joints were evaluated postmortem using magnetic resonance imaging (MRI) and histology. Proteomics identified 40 proteins for which abundance was significantly correlated between serum and synovial fluid, including markers of inflammatory joint disease and lysosomal dysfunction. Elevated expression of three biomarker candidates, matrix metalloproteinase 19, inter-alpha-trypsin inhibitor heavy-chain 3 and alpha-1-microglobulin, was confirmed in MPS I cartilage, and serum abundance of these molecules was found to correlate with MRI and histological degenerative grades. The candidate biomarkers identified in this study have the potential to improve patient care by facilitating minimally-invasive, specific assessment of joint disease severity, progression and response to therapeutic intervention.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

TISSUE(S): Blood Plasma

SUBMITTER: Hossein Fazelinia  

LAB HEAD: Lachlan J. Smith, Ph.D.

PROVIDER: PXD037130 | Pride | 2024-05-22

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20210527_115607_LS1548_dDIA.sne Other
20210729_100120_LS1573_serum_dDIA.sne Other
checksum.txt Txt
q210523_LS1548_DIA3_01.raw Raw
q210523_LS1548_DIA3_02.raw Raw
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Publications

Proteomics identifies novel biomarkers of synovial joint disease in a canine model of mucopolysaccharidosis I.

Zhang Chenghao C   Gawri Rahul R   Lau Yian Khai YK   Spruce Lynn A LA   Fazelinia Hossein H   Jiang Zhirui Z   Jo Stephanie Y SY   Scanzello Carla R CR   Mai Wilfried W   Dodge George R GR   Casal Margret L ML   Smith Lachlan J LJ  

Molecular genetics and metabolism 20230104 2


Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this  ...[more]

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