Bibliographic Details
| Title: |
Therapeutic blockade of CCL17 in obesity-exacerbated osteoarthritic pain and disease. |
| Authors: |
Lee, Kevin Ming-Chin1 (AUTHOR) mingchinl@unimelb.edu.au, Lupancu, Tanya1 (AUTHOR), Keenan, Stacey N.2 (AUTHOR), Bing, Georgina3 (AUTHOR), Achuthan, Adrian A.1 (AUTHOR), Biondo, Mark3 (AUTHOR), Lieu, Kim Gia3 (AUTHOR), Watt, Matthew J.2 (AUTHOR), Maraskovsky, Eugene3 (AUTHOR), Kingwell, Bronwyn A.3 (AUTHOR), Hamilton, John A.1 (AUTHOR) |
| Source: |
PLoS ONE. 1/16/2025, Vol. 20 Issue 1, p1-14. 14p. |
| Subject Terms: |
*GLUCOSE tolerance tests, *HIGH-fat diet, *INSULIN resistance, *JOINT injuries, *TREATMENT effectiveness |
| Abstract: |
Objectives: We previously reported that CCL17 gene-deficient mice are protected from developing pain-like behaviour and exhibit less disease in destabilization of medial meniscus (DMM)-induced OA, as well as in high-fat diet (HFD)-exacerbated DMM-induced OA. Here, we explored if therapeutic neutralization of CCL17, using increasing doses of a neutralizing monoclonal antibody (mAb), would lead to a dose-dependent benefit in these two models. Design: DMM-induced OA was initiated in male mice either fed with a control diet (7% fat) or 8 weeks of a 60% HFD, followed by therapeutic intraperitoneal administration (i.e. when pain is evident) of an anti-CCL17 mAb (B293, 25mg/kg, 5mg/kg or 1mg/kg) or isotype control (BM4; 25mg/kg). Pain-like behaviour and arthritis were assessed by relative static weight distribution and histology, respectively. The effects of B293 (25mg/kg) on HFD-induced metabolic changes, namely oral glucose tolerance test, insulin tolerance test and liver triglyceride levels, were examined. Results: Therapeutic administration of B293 results in a dramatic amelioration of DMM-induced OA pain-like behaviour and the inhibition of disease progression, compared to BM4 (isotype control) treatment. A similar therapeutic effect was observed in HFD-exacerbated OA pain-like behaviour and disease. B293 treatment did not alter the measured HFD-induced metabolic changes. Conclusions: Based on the data presented, CCL17 could be a therapeutic target in OA patients with joint injury alone or with obesity. [ABSTRACT FROM AUTHOR] |
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