Journal
BONE
Volume 48, Issue 6, Pages 1362-1369Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2011.03.773
Keywords
Osteoprotegerin; Intervertebral disc; Cartilage endplate; Osteoclast; Intervertebral disc degeneration
Categories
Funding
- National Science Fund for Distinguished Young Scholars [30625043]
- National Natural Science Foundation of China [30710103904, 30930111, 30973760, 30901914, 30600829, 30701118, 30572398]
- National Basic Research Program of China (973 Program) [2010CB530400]
- Chinese Science and Technology Committee Emphasis [2006DFA32670]
- Changjiang Scholar Chair Professor project [(2009) 17]
- Shanghai Medical leading talent support scheme [LJ06018]
- Shanghai Education Innovation Project [08YZ56]
- Shanghai Science and Technology Commission [07JC14050]
- Shanghai Youth Science and Technology Development plan project [07QA14051, 09QA1405600]
- Shanghai Education Commission, Division 6
- Ministry of Education [20070268004]
- Modernization of Chinese medicine-Shanghai Science and Technology Commission [09dZ1977200]
- Shanghai University [szy09021]
- Natural Science Foundation of Shanghai [11ZR1437100]
- National Institutes of Health [AR48697]
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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 20 weeks 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. (C) 2011 Elsevier Inc. All rights reserved.
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