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

Gang Xu; Jian Wang; Long Ma; Xin Zhao; Wen Luo; Qunhua Jin

doi:10.1080/08916934.2019.1643844

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

Autoimmunity. 2019 Jun;52(4):168-175. doi: 10.1080/08916934.2019.1643844. Epub 2019 Aug 13.

Authors

Gang Xu¹, Jian Wang¹, Long Ma^{1

2}, Xin Zhao^{1

2}, Wen Luo¹, Qunhua Jin^{1

2}

Affiliations

¹ The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China.
² Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , PR China.

PMID: 31407595
DOI: 10.1080/08916934.2019.1643844

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.

Keywords: DMM; NLRP3; OA; Rapamycin; autophagy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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*
Osteoarthritis / pathology*
Osteoarthritis / prevention & control
Sirolimus / therapeutic use*

Substances

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