Local intra-articular injection of rapamycin inhibits NLRP3 activity and prevents osteoarthritis in mouse DMM models.

Abstract	This study investigated the influence of autophagy on the expression of Collagen type II and light chain 3 (LC-3) in the articular cartilage of osteoarthritis (OA) models. The expression of OA associated biomarkers namely Matrix metalloproteinase (MMP-13), NOD-, LRR- and pyrin domain-containing 3 (NLRP3) induced by destabilizing the medial meniscus operation (DMM) were also investigated. A total of 60 C57BL/6 mice were divided into (1) control; (2) DMM2; (3) DMM8; (4) rapamycin 2 weeks; and (5) rapamycin 8 weeks groups. Saffranin O-Fast green staining, histomorphometry and immunohistochemical methods were used for analysis. In the DMM group, the expression of the OA biomarkers MMP-13, NLRP3 significantly increased, whilst Collagen II and LC-3B levels were significantly lower than other experimental groups. We hypothesized that NLRP3 inhibits autophagy activation and delays disease progression.
Authors	Gang Xu, Jian Wang, Long Ma, Xin Zhao, Wen Luo, Qunhua Jin
Journal	Autoimmunity (Autoimmunity) Vol. 52 Issue 4 Pg. 168-175 (06 2019) ISSN: 1607-842X [Electronic] England
PMID	31407595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Collagen Type II Immunosuppressive Agents Map1lc3b protein, mouse Microtubule-Associated Proteins NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Matrix Metalloproteinase 13 Mmp13 protein, mouse Sirolimus
Topics	Animals Autophagy (physiology) Cartilage, Articular (pathology) Collagen Type II (biosynthesis) Immunosuppressive Agents (therapeutic use) Male Matrix Metalloproteinase 13 (metabolism) Menisci, Tibial (pathology) Mice Mice, Inbred C57BL Mice, Inbred NOD Microtubule-Associated Proteins (biosynthesis) NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors) Osteoarthritis (drug therapy, pathology, prevention & control) Sirolimus (therapeutic use)

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