The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice

Qian Qian Liang, Xiao Feng Li, Quan Zhou, Lianping Xing, Shao Dan Cheng, Dao Fang Ding, Le Qin Xu, De Zhi Tang, Qin Bian, Zhi Jie Xi, Chongjian Zhou, Qi Shi, Yong Jun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Human chondrocytes and annulus fibrosus cells of intervertebral disc (IVD) express osteoprotegerin (OPG), but the effect of OPG on the pathogenesis of IVD degeneration remains unknown. Here we assessed the phenotype change of IVD in OPG-/- mice. Methods: The IVDs from 12-, 20-, and 28-week-old OPG-/- mice and WT controls were subjected to histologic analyses including TRAP staining for osteoclasts, immunostaining for OPG and type I collagen protein expression, and TUNEL staining for apoptosis. The IVD tissues were also subjected to real time RT-PCR for mRNA expression of genes for osteoblast-osterix, ALP, and osteocalcin; for osteoclasts-trap, rank, mmp9 and cathepsin K, and for chondrocytes-aggrecan, mmp13 and Col10. Results: OPG protein expresses at the cells of endplate cartilage and annulus fibrosis in IVDs of WT mice. Compared to WT mice, OPG-/- mice developed aging related cartilage loss and bony tissue appearance at the endplate. Stating from 20weeks of age, IVDs from OPG-/- mice expressed significantly increased mmp13 and Col10 levels, which is associated with increased osteoblast number and elevated expression of osteoblast marker genes. Furthermore, TRAP+ osteoclasts were presented in the endplate cartilage of OPG-/- mice. These osteoclasts localized adjacently to and erosion into the cartilage. Increased expression of RANK, mmp9 and cathepsin k was detected in OPG-/- IVDs. Conclusions: OPG at IVD plays an important role for maintaining the integrity of endplate cartilage during aging by preventing endplate cartilage from osteoclast-mediated resorption.

Original languageEnglish (US)
Pages (from-to)1362-1369
Number of pages8
JournalBone
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Keywords

  • Cartilage endplate
  • Intervertebral disc
  • Intervertebral disc degeneration
  • Osteoclast
  • Osteoprotegerin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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