Dataset Information

Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR.

ABSTRACT:

Background

It is generally thought that the occurrence and progression of osteoarthritis (OA) results from multiple causes, including degradation and destruction of the cartilage matrix and aging of chondrocytes. Metformin is a first-line drug for the treatment of diabetes, and has great potential for the treatment of other disorders. However, the role of metformin in OA is unknown.

Results

Metformin displayed a protective effect against OA. There were lower OARSI scores and fewer MMP-13-positive cells in DMM mice and cartilage explants after treatment with metformin. In addition, metformin treatment decreased p16^INK4a levels in OA chondrocytes, and enhanced polarization of AMPK and inhibition of mTORC1 in OA mice and chondrocytes in a dose-dependent manner.

Conclusions

Metformin effectively alleviated cartilage degradation and aging through regulation of the AMPK/mTOR signaling pathways, suggesting that it could be an effective treatment for OA.

Methods

The effects of metformin on cartilage degradation and chondrocyte aging was determined in a destabilization of the medial meniscus (DMM)-induced OA mouse model and in IL-1?-treated mouse chondrocytes and cartilage explants. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI) criteria. Immunostaining, RT-PCR, and western blot analyses were conducted to detect the relative expressions of protein and RNA.

SUBMITTER: Feng X

PROVIDER: S-EPMC7053618 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR.

Feng Xiaofeng X Pan Jianying J Li Junyan J Zeng Chun C Qi Weizhong W Shao Yan Y Liu Xin X Liu Liangliang L Xiao Guozhi G Zhang Haiyan H Bai Xiaochun X Cai Daozhang D

Aging 20200116 2

<h4>Background</h4>It is generally thought that the occurrence and progression of osteoarthritis (OA) results from multiple causes, including degradation and destruction of the cartilage matrix and aging of chondrocytes. Metformin is a first-line drug for the treatment of diabetes, and has great potential for the treatment of other disorders. However, the role of metformin in OA is unknown.<h4>Results</h4>Metformin displayed a protective effect against OA. There were lower OARSI scores and fewer ...[more]

PMID: 31945013

Similar Datasets

Project description:Mesenchymal stem cell (MSC)-based cell therapy is a promising avenue for osteoarthritis (OA) treatment. In the present study, we evaluated the efficacy of intra-articular injections of culture-expanded allogenic adipose tissue-derived stem cells (ADSCs) for the treatment of anterior cruciate ligament transection (ACLT) induced rat OA model. The paracrine effects of major histocompatibility complex (MHC)-unmatched ADSCs on chondrocytes were investigated in vitro. Rats were divided into an OA group that underwent ACLT surgery and a sham-operated group that did not undergo ACLT surgery. Four weeks after surgery mild OA was induced in the OA group. Subsequently, the OA rats were randomly divided into ADSC and control groups. A single dose of 1 × 106 ADSCs suspended in 60 μL phosphate-buffered saline (PBS) was intra-articularly injected into the rats of the ADSC group. The control group received only 60 μL PBS. OA progression was evaluated macroscopically and histologically at 8 and 12 weeks after surgery. ADSC treatment did not cause any adverse local or systemic reactions. The degeneration of articular cartilage was significantly weaker in the ADSC group compared to that in the control group at both 8 and 12 weeks. Chondrocytes were co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1β-induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and MMP-13 and the pro-inflammatory cytokines TNF-α and IL-6 in chondrocytes. Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL-10 in chondrocytes. The results of this study indicated that the intra-articular injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration in an experimental rat OA model without inducing any adverse reactions. MHC-unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage. The paracrine effects of ADSCs on OA chondrocytes are at least part of the mechanism by which ADSCs exert their therapeutic activity.

Dataset Information

Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR.

Background

Results

Conclusions

Methods

Publications

Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets