Osteogenic protein-1 attenuates apoptosis and enhances matrix synthesis of nucleus pulposus cells under high magnitude compression though inhibiting the p38 MAPK pathway

Abstract

Disc degeneration is correlated with mechanical load. Osteogenic protein-1 (OP-1) is potential to regenerate degenerative disc. To investigate whether OP-1 can protect against high magitude compression-induced nucleus pulposus (NP) cell apoptosis and NP matrix catabolism, and its potential mechanism; porcine discs were cultured in a bioreactor and compressed at a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days. OP-1 was added along with the culture medium to investigate the protective effects of OP-1. NP cell apoptosis and matrix biosynthesis were evaluated. Additionally, activity of the p38 MAPK pathway is also analyzed. Compared with the control group, high magnitude compression significantly promoted NP cell apoptosis and decreased NP matrix biosynthesis, reflected by the increase in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and caspase-3 activity, the up-regulated expression of Bax and caspase-3 mRNA and down-regulated expression of Bcl-2 mRNA, and the decreased Alcian Blue staining intensity and expression of matrix proteins (aggrecan and collagen II). However, OP-1 addition partly attenuated the effects of high magnitude compression on NP cell apoptosis and NP matrix biosynthesis. Further analysis showed that inhibition of the p38 MAPK pathway partly participated in this process. OP-1 can attenuate high magnitude compression-induced NP cell apoptosis and promoted NP matrix biosynthesis, and inhibition of the p38 MAPK pathway may participate in this regulatory process. The present study provides that OP-1 may be efficient in retarding mechanical overloading-exacerbated disc degeneration.

Mechano growth factor attenuates mechanical overload-induced nucleus pulposus cell apoptosis through inhibiting the p38 MAPK pathway

“…A decrease in the NP cell density caused by cell apoptosis is an important cellular pathology during disc degeneration [11]. As an important initiator of disc degeneration, mechanical overload has been reported to be closely related with disc cell apoptosis and thus contributes to disc degeneration [5,22–24]. Therefore, inhibition of mechanical overload-induced disc cell apoptosis may be a potential treatment of disc degeneration.…”

Rosuvastatin: A Potential Therapeutic Agent for Inhibition of Mechanical Pressure-Induced Intervertebral Disc Degeneration

“…Although certain MP can promote the division and proliferation of NPCs, excessive MP can also inhibit the proliferation of NPCs and even induce apoptosis of NPCs. 20 Ultimately, this leads to fibrosis of the medullary tissue, which changes from a translucent gel to a firmer cartilaginous tissue and loses its normal function. In summary, our findings reveal the effect of MP on the proliferative activity and wound healing ability of NPCs within IVDs.…”

Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway

“…Moreover, previous research has shown that mechanical stress stimulation causes IDD and that p38 MAPK is involved in that process (Studer et al, 2007;Pang et al, 2017). On this basis, Fang et al (Fang et al, 2018) found that the p38 MAPK pathway activity was significantly increased under high-intensity compression, and the activity was significantly decreased after adding osteogenic protein-1 (OP-1). In addition, adding OP-1 when culturing NPCs could reduce NP cell apoptosis and enhance matrix synthesis.…”