GPR120 is an important inflammatory regulator in the development of osteoarthritis

Yuanfeng Chen,Gang Li,Huantian Zhang,Zhengang Zha,Wade Chun-Wai Suen,Dan Zhang,Ki Wai Ho,Sien Lin,Po Sing Leung

doi:10.1186/s13075-018-1660-6

Abstract

BackgroundThe aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA).MethodsGPR120 knockout (KO) and wild-type (WT) mice were used to create an animal model of OA by means of anterior cruciate ligament transection (ACLT) surgery. The severity of OA was staged and evaluated by histological examination, microcomputed tomography scan and enzyme-linked immunosorbent assay (ELISA). The anti-inflammatory effects of the GPR120 agonist docosahexaenoic acid (DHA) on human chondrocytes were further evaluated by specific inflammatory markers. In addition, the healing progression of a skin defect model was determined with histological assays.ResultsThe GPR120-KO mice displayed an accelerated development of OA after ACLT. The secondary inflammation, cartilage degeneration, and subchondral bone aberrant changes were significantly elevated in the early phase of OA in KO mice relative to those in WT mice. In addition, we found that GPR120 levels were downregulated in OA patients compared with control subjects, whereas GPR120 activation with DHA exhibited anti-inflammatory effects in primary human chondrocytes in vitro. Moreover, results from the skin defect model showed that GPR120 agonism with DHA enhanced wound repair in mice, as shown by the downregulation of the number of CD68+ cells.ConclusionsOur study suggests that GPR120 is an important inflammatory mediator during the development of OA, and that it is a potential marker for the diagnosis of high-risk patients with OA.

Highlights

The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA)
Validation of GPR120-KO mice Genotyping result showed that only WT mice showed expression of GPR120 at the genomic DNA (Fig. 1a) or mRNA level (Fig. 1b, c), while such expression was not detected in GPR120-KO mice. β-galactosidase activity is a surrogate of GPR120, and immunofluorescent staining showed that β-galactosidase-positive cells could be found in colon tissue of the KO mice while it was absent in WT mice (Fig. 1d)
Acceleration of cartilage degeneration in GPR120-KO mice with surgically induced OA Safranin-O/fast green staining showed that there were significantly more degenerative features in the knee joint samples of KO mice compared with those of WT mice at 4 weeks postoperation, while the cartilage damage is obvious in both groups 6 weeks after the OA surgery

Summary

Introduction

The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA). The circulating FAs can serve as either proinflammatory or anti-inflammatory molecules for metabolic signaling; for example, the saturated FAs can activate macrophages to secrete tumor necrosis factor (TNF)-α and interleukin (IL)-1, thereby activating the proinflammatory pathways [5] In this regard, the derivatives of ω-6 polyunsaturated FAs (PUFA) are involved in joint pain [6, 7], while ω-3 FAs are reported to reduce spontaneous OA in animals on a low-fat diet [8]. Changes in the composition of this lubrication layer due to either injury or abnormal lipid metabolism may impact the function of the articular joint and potentially lead to the onset of OA [11] These findings imply that free FAs or metabolic factors play a relatively direct role in the process of joint degeneration, but the regulatory roles of the ω-3 FAs and their receptors in the development of OA still need to be further investigated

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