Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level

Liu,Heng; Li,Zhuoyang; Cao,Yongping; Cui,Yunpeng; Yang,Xin; Meng,Zhichao; Wang,Rui

doi:10.3892/mmr.2019.10559

Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level

Authors:
- Heng Liu
- Zhuoyang Li
- Yongping Cao
- Yunpeng Cui
- Xin Yang
- Zhichao Meng
- Rui Wang
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Affiliations: Department of Orthopedics, Peking University First Hospital, Beijing 100034, P.R. China
Published online on: August 6, 2019 https://doi.org/10.3892/mmr.2019.10559
Pages: 3308-3316
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies identified that chondrocyte apoptosis serves an important role in osteoarthritis (OA). However, the mechanisms of cartilage degeneration induced by apoptosis remain unclear. The present study investigated the role of mitochondrial dysfunction in OA pathology. A total of 30 cartilage samples presenting an Outerbridge score ranging between 0 and III were collected during total knee arthroplasty. Half of the samples were embedded for observation by transmission electron microscopy. The remaining samples were digested, and chondrocytes were isolated from normal and OA tissues. Subsequently, the enzymatic activity of factors of the mitochondrial respiratory chain (MRC), and mitochondrial membrane potential (Δψm), were quantified. Furthermore, chondrocytes were treated with rotenone (Ro), a specific inhibitor of the MRC, and curcumin (Cur), a mitochondrial protective agent, with the aim of analyzing the relationship between mitochondrial dysfunction and chondrocyte apoptosis. The mitochondria of OA chondrocytes showed apoptosis‑associated morphological alterations compared with normal cells. The Δψm and the activity of MRC enzymes were decreased in OA chondrocytes. Moreover, compared with normal chondrocytes, treatment with Ro was able to induce morphological changes reminiscent of the phenotype observed in OA chondrocytes. Additionally, Ro inhibited cellular proliferation, increased the apoptotic rate, and decreased the Δψm and the secretion of type II collagen. Furthermore, Cur could partly reverse the effects caused by treatment with Ro. The present data suggested that mitochondrial function was impaired in OA chondrocytes, resulting in an increased chondrocyte apoptosis and decreased type II collagen secretion. In addition, treatment with Cur protected the mitochondrial function and prevented cartilage degeneration. Collectively, the present results suggested that mitochondrial dysfunction may aggravate cartilage degeneration in the pathogenesis of OA.

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