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

Yi Jie Kuo, Lien Chen Wu, Jui Sheng Sun, Ming Hong Chen, Man Ger Sun, Yang Hwei Tsuang

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalJournal of Orthopaedic Science
Volume19
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Mechanical Stress
Bone Morphogenetic Protein 7
Bone Morphogenetic Protein 2
Apoptosis
Platelet-Derived Growth Factor
Somatomedins
Cytokines
Intervertebral Disc Degeneration
In Situ Nick-End Labeling
Tail
Spine
Necrosis
In Vitro Techniques
Nucleus Pulposus
Gene Expression

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Medicine(all)

Cite this

Mechanical stress-induced apoptosis of nucleus pulposus cells : An in vitro and in vivo rat model. / Kuo, Yi Jie; Wu, Lien Chen; Sun, Jui Sheng; Chen, Ming Hong; Sun, Man Ger; Tsuang, Yang Hwei.

In: Journal of Orthopaedic Science, Vol. 19, No. 2, 2014, p. 313-322.

Research output: Contribution to journalArticle

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AU - Tsuang, Yang Hwei

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AB - 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.

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