Osteogenic protein-1 alleviates high glucose microenvironment-caused degenerative changes in nucleus pulposus cells.

Ziming Liu,Yongqiang Zhang,Jiagang Xu,Wennan Du,Qi Tan,Ali Zhang,Rongfeng Zhang,Xiangkun Wu,Zhiwen Zhang,Wei Huang,Chengmin Zhang,Fan Zhang,Ning Li

doi:10.1042/bsr20190170

Abstract

Increasing evidence has indicated a close relationship between diabetes mellitus (DM) and disc degeneration. As a potential therapeutic growth factor, osteogenic protein-1 (OP-1) has lots of protective effects on the healthy disc cell’s biology. The present study was aimed to investigate the effects of OP-1 on degenerative changes of nucleus pulposus (NP) cells in a high glucose culture. Rat NP cells were cultured in the baseline medium or the high glucose (0.2 M) culture medium. OP-1 was added into the high glucose culture medium to investigate whether its has some protective effects against degenerative changes of NP cells in the high glucose culture. NP cell apoptosis ratio, caspase-3/9 activity, expression of apoptosis-related molecules (Bcl-2, Bax, and caspase-3), matrix macromolecules (aggrecan and collagen II), and matrix remodeling enzymes (MMP-3, MMP-13, and ADAMTS-4), and immuno-staining of NP matrix proteins (aggrecan and collagen II) were evaluated. Compared with the baseline culture, high glucose culture significantly increased NP cell apoptosis ratio, caspase-3/9 activity, up-regulated expression of Bax, caspase-3, MMP-3, MMP-13 and ADAMTS-4, down-regulated expression of Bcl-2, aggrecan and collagen II, and decreased staining intensity of aggrecan and collagen II. However, the results of these parameters were partly reversed by the addition of OP-1 in the high glucose culture. OP-1 can alleviate high glucose microenvironment-induced degenerative changes of NP cells. The present study provides that OP-1 may be promising in retarding disc degeneration in DM patients.

Highlights

IntroductionIntervertebral disc degeneration, occurring in ∼40% of these cases, is regarded as a main contributor to low back pain [1]
Low back pain is a common musculoskeletal disease around the world
The cell apoptosis ratio was partly decreased when osteogenic protein-1 (OP-1) was added into the high glucose culture medium (Figure 1)

Summary

Introduction

Intervertebral disc degeneration, occurring in ∼40% of these cases, is regarded as a main contributor to low back pain [1]. The number of patients with intervertebral disc degeneration is increasing due to the population ageing in the world, which causes lots of medical spending [2]. Previous studies have shown that glucose-mediated oxidative stress injury is associated with hyperglycemia [13,14]. Oxidative stress injury caused by the increase in intracellular reactive oxygen species (ROS) seriously and negatively affects disc cell biology [3,15,16,17]. Inhibition of high glucose environment-induced harmful effects may be important in retarding disc degeneration in DM patients

Methods

Results

Conclusion