Effects of UCP4 on the Proliferation and Apoptosis of Chondrocytes: Its Possible Involvement and Regulation in Osteoarthritis

Zhongming Huang; Junhua Li; Shaohua Du; Guangnan Chen; Yiying Qi; Ligang Huang; Luwei Xiao; Peijian Tong

doi:10.1371/journal.pone.0150684

Effects of UCP4 on the Proliferation and Apoptosis of Chondrocytes: Its Possible Involvement and Regulation in Osteoarthritis

PLoS One. 2016 Mar 2;11(3):e0150684. doi: 10.1371/journal.pone.0150684. eCollection 2016.

Authors

Zhongming Huang^{1

2

3

4}, Junhua Li^{1

2}, Shaohua Du⁵, Guangnan Chen⁵, Yiying Qi⁵, Ligang Huang³, Luwei Xiao^{3

4

6}, Peijian Tong^{3

4

6}

Affiliations

¹ Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, China.
² Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
³ Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, China.
⁵ Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁶ Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Abstract

Reactive oxygen species (ROS)-induced chondrocytes apoptosis plays a key role in osteoarthritis (OA) pathogenesis. Uncoupling protein 4 (UCP4) can protect cells against oxidative stress via reducing ROS production and cell apoptosis. Here, silencing of UCP4 in primary chondrocytes significantly inhibited cell survival, but induced ROS production and cell apoptosis. UCP4 mRNA of cartilage tissues was decreased in osteoarthritis patients, which was negatively correlated with synovial fluid (SF) leptin concentration. Moreover, leptin treatment (5, 10 and 20 ng/ml) of primary cultured chondrocytes significantly decreased mRNA and protein levels of UCP4, but increased ROS production and cell apoptosis in a dose-dependent manner. The effects of leptin treatment (20 ng/ml) on chondrocytes was partially reversed by ectopic expression of UCP4. More importantly, intraarticularly injection of UCP4 adenovirus remarkably alleviate OA progression and cell apoptosis in a rat OA model induced by anterior cruciate ligament transection (ACLT). In conclusion, UCP4, whose expression was suppressed by leptin, may be involved in the ROS production and apoptosis of chondrocytes, thus contributing to the OA pathogenesis.

Publication types

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

MeSH terms

Adult
Aged
Animals
Apoptosis*
Cartilage, Articular / metabolism
Cartilage, Articular / pathology
Cell Proliferation
Cells, Cultured
Chondrocytes / metabolism
Chondrocytes / pathology*
Down-Regulation*
Humans
Ion Channels / genetics*
Ion Channels / metabolism
Leptin / metabolism
Male
Membrane Potential, Mitochondrial
Membrane Transport Proteins / genetics*
Membrane Transport Proteins / metabolism
Middle Aged
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Mitochondrial Uncoupling Proteins
Osteoarthritis / genetics*
Osteoarthritis / metabolism
Osteoarthritis / pathology
RNA Interference
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism

Substances

Ion Channels
Leptin
Membrane Transport Proteins
Mitochondrial Proteins
Mitochondrial Uncoupling Proteins
RNA, Messenger
RNA, Small Interfering
Reactive Oxygen Species
SLC25A27 protein, human
Slc25a27 protein, rat

Grants and funding

The work was supported by the Science Technology Program of Zhejiang Province (2013C33096), the Key Medical Disease Program of Hangzhou city (20120533Q39, 2013B51), the TCM Foundation for Distinguished Young Talents of Zhejiang Province (2012ZQ023, 2012ZQ024), the Key Science Technology Program of Xiaoshan district (2012234) and the Medical Disease Program of Zhejiang Province (2012KYB169, 2013KYB226). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.