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Published on: March 18, 2022
Deletion of Dual Specificity Phosphatase 1 Does Not Predispose Mice to Increased Spontaneous Osteoarthritis
Michael Andrew Pest1, Courtney Alice Pest1, Melina Rodrigues Bellini1
1Department of Physiology and Pharmacology, Western University, London, ON, Canada.
Background:
Osteoarthritis (OA) is a degenerative joint disease with poorly understood etiology and pathobiology. Mitogen activated protein kinases (MAPKs) including ERK and p38 play important roles in the mediation of downstream pathways involved in cartilage degenerative processes. Dual specificity phosphatase 1 (DUSP1) dephosphorylates the threonine/serine and tyrosine sites on ERK and p38, causing deactivation of downstream signalling. In this study we examined the role of DUSP1 in spontaneous OA development at 21 months of age using a genetically modified mouse model deficient in Dusp1 (DUSP1 knockout mouse).
Results:
Utilizing histochemical stains of paraffin embedded knee joint sections in DUSP1 knockout and wild type female and male mice, we showed similar structural progression of cartilage degeneration associated with OA at 21 months of age. A semi-quantitative cartilage degeneration scoring system also demonstrated similar scores in the various aspects of the knee joint articular cartilage in DUSP1 knockout and control mice. Examination of overall articular cartilage thickness in the knee joint demonstrated similar results between DUSP1 knockout and wild type mice. Immunostaining for cartilage neoepitopes DIPEN, TEGE and C1,2C was similar in the cartilage lesion sites and chondrocyte pericellular matrix of both experimental groups. Likewise, immunostaining for phosphoERK and MMP13 showed similar intensity and localization between groups. SOX9 immunostaining demonstrated a decreased number of positive cells in DUSP1 knockout mice, with correspondingly decreased staining intensity. Analysis of animal walking patterns (gait) did not show a discernable difference between groups.
Conclusion:
Loss of DUSP1 does not cause changes in cartilage degeneration and gait in a mouse model of spontaneous OA at 21 months of age. Altered staining was observed in SOX9 immunostaining which may prove promising for future studies examining the role of DUSPs in cartilage and OA, as well as models of post-traumatic OA.
Insights
Loss of Dual Specificity Phosphatase 1 (DUSP1) did not affect cartilage degeneration or gait in aged mice with osteoarthritis (OA). Further research into DUSP1
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease with complex etiology.
- Mitogen-activated protein kinases (MAPKs), including ERK and p38, are implicated in cartilage degradation.
- Dual Specificity Phosphatase 1 (DUSP1) deactivates ERK and p38 signaling pathways.
Purpose of the Study:
- To investigate the role of DUSP1 in the spontaneous development of OA.
- To analyze OA progression in DUSP1-deficient mice at 21 months of age.
Main Methods:
- Histochemical staining of knee joint sections from DUSP1 knockout and wild-type mice.
- Semi-quantitative scoring of cartilage degeneration and measurement of cartilage thickness.
- Immunostaining for cartilage neoepitopes, phospho-ERK, MMP13, and SOX9.
- Gait analysis to assess locomotion.
Main Results:
- No significant differences in cartilage degeneration, structural progression, or thickness between DUSP1 knockout and wild-type mice.
- Similar levels of cartilage neoepitopes (DIPEN, TEGE, C1,2C), phospho-ERK, and MMP13.
- Decreased SOX9-positive cells and staining intensity observed in DUSP1 knockout mice.
- No discernible differences in gait patterns between the experimental groups.
Conclusions:
- DUSP1 deficiency does not influence spontaneous OA development or gait in mice at 21 months.
- Altered SOX9 staining suggests a potential role for DUSP1 in chondrocyte regulation.
- Findings warrant further investigation into DUSP1's role in OA pathogenesis and post-traumatic OA models.
