Antiosteoarthritic Effect of Morroniside in Chondrocyte Inflammation and Destabilization of Medial Meniscus-Induced Mouse Model.

Eunkuk Park,Jeonghyun Kim,Seung Hee Yun,Chang Gun Lee,Hyoju Jeon,Siyoung Yang,Seong Jae Han,Seon-Yong Jeong,Seokjin Hwang,Chun Whan Choi

doi:10.3390/ijms22062987

Abstract

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1β)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1β-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.

Highlights

Osteoarthritis (OA) is a complex chronic disease and one of the most common types of arthritis, resulting in cartilage loss, pain, and stiffness [1,2]
The Cornus officinalis (CO) extract did not affect cell viability (Supplementary Figure S1A). These results indicate that the CO extract possesses anti-inflammatory activity against chondrocyte inflammation
Morroniside treatment reduced IL-1β-mediated upregulation of prostaglandin E2 (PGE2) and collagenase levels in primary chondrocytes (Figure 4). These results indicate that morroniside prevents OA pathogenesis by reducing PGE2 and collagenase secretion

Summary

Introduction

Osteoarthritis (OA) is a complex chronic disease and one of the most common types of arthritis, resulting in cartilage loss, pain, and stiffness [1,2]. The early onset of OA is initiated by mechanical stress in the articular cartilage, resulting in an excessive level of interleukin-1 beta (IL-1β) in the superficial zone of the cartilage [4,5]. Excessive levels of IL-1β trigger joint damage and inflammation via the upregulation of OA-inducing factors such as cyclooxygenase-2 (Cox-2) and matrix metalloproteinase (Mmp) [6,7]. These inflammatory mediators suppress collagen synthesis in chondrocytes following stimulation with prostaglandin E2 and collagenase secretion [8].

Objectives

Methods

Results

Conclusion