Mechanical stress-induced apoptosis of nucleus pulposus cells: an in vitro and in vivo rat model.

Abstract

BACKGROUND:

Un-physiological loads play an important role in the degenerative process of inter-vertebral discs (IVD). In this study, we used an in vitro and in vivo rat model to investigate the mechanism of nucleus pulposus (NP) cells apoptosis induced by mechanical stress.

METHODS:

Static compressive load to IVDs of rat tails was used as the in vivo model. For the in vitro model, NP cells were tested under the physiological and un-physiological loading. For histological examination, apoptotic index study, and apoptotic gene expression, we also selected cytokines [bone morphogenetic protein (BMP)-2/7, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)] to be analyzed.

RESULTS:

Under mechanical loading, cellular density was significantly decreased, but there was an increase of TUNEL positive cells and apoptosis index. In a dose-dependent manner; the necrosis became apparent in the un-physiologic strain. The selected cytokines (BMP-2/7, IGF-1, PDGF) can significantly reduce the percentage of apoptotic and necrotic cells.

CONCLUSIONS:

We conclude that the intrinsic (mitochondrial) apoptotic pathway plays an important role in the compressive load-induced apoptosis of NP cells. Combination therapy reducing the mechanical load and selected cytokines (BMP-2/7, IGF-1 and PDGF) may have considerable promise in the treatment of spine disc degeneration.

• Authors: Yi-Jie Kuo, Lien-Chen Wu, Jui-Sheng Sun, Ming-Hong Chen, Man-Ger Sun, Yang-Hwei Tsuang
• Journal: Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association (J Orthop Sci) Vol. 19 Issue 2 Pg. 313-322 (Mar 2014) ISSN: 1436-2023 [Electronic] Japan
• PMID: 24338049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Morphogenetic Protein 2
• Cytokines
• RNA

Topics

• Animals
• Apoptosis (physiology)
• Bone Morphogenetic Protein 2 (biosynthesis, genetics)
• Cells, Cultured
• Cytokines (biosynthesis, genetics)
• Disease Models, Animal
• Flow Cytometry
• Fractures, Compression (genetics, metabolism, pathology)
• Gene Expression Regulation
• Immunohistochemistry
• Intervertebral Disc (injuries, metabolism, pathology)
• RNA (genetics)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Stress, Mechanical
• Tail (injuries, pathology)