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

doi:10.1016/j.bone.2011.03.773

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 journal › Article › peer-review

14 Scopus citations

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 language	English (US)
Pages (from-to)	1362-1369
Number of pages	8
Journal	Bone
Volume	48
Issue number	6
DOIs	https://doi.org/10.1016/j.bone.2011.03.773
State	Published - Jun 1 2011
Externally published	Yes

Keywords

Cartilage endplate
Intervertebral disc
Intervertebral disc degeneration
Osteoclast
Osteoprotegerin

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Physiology
Histology

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10.1016/j.bone.2011.03.773

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@article{23998d99d4e9474b919a9b900b673795,

title = "The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice",

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.",

keywords = "Cartilage endplate, Intervertebral disc, Intervertebral disc degeneration, Osteoclast, Osteoprotegerin",

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

note = "Funding Information: This work was supported by the National Science Fund for Distinguished Young Scholars ( 30625043 ), the International Cooperation Programs of National Natural Science Foundation of China ( 30710103904 ), National Basic Research Program of China (973 Program 2010CB530400 ), the International Technical Cooperation Key Project Plan, Chinese Science and Technology Committee Emphasis ( 2006DFA32670 ), the Project of National Natural Science Foundation of China ( 30930111 , 30973760 , 30901914 , 30600829 , 30701118 and 30572398 ), Changjiang Scholar Chair Professor project (Teach people (2009) 17), Shanghai Medical leading talent support scheme ( LJ06018 ), Shanghai Education Innovation Project ( 08YZ56 ), The basic key project of Shanghai Science and Technology Commission ( 07JC14050 ), Shanghai Youth Science and Technology Development plan project ( 07QA14051 , 09QA1405600 ), Shanghai University Innovation Team Programme (Shanghai Education Commission, Division 6 (2009)), The Ministry of Education Doctoral Fund ( 20070268004 ), Modernization of Chinese medicine-Shanghai Science and Technology Commission special ( 09dZ1977200 ), Shanghai University Select and Train Outstanding Young Teachers in Special Fund ( szy09021 ), Natural Science Foundation of Shanghai ( 11ZR1437100 ), National Institutes of Health PHS awards ( AR48697 to LX).",

year = "2011",

month = jun,

day = "1",

doi = "10.1016/j.bone.2011.03.773",

language = "English (US)",

volume = "48",

pages = "1362--1369",

journal = "Bone",

issn = "8756-3282",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice

AU - Liang, Qian Qian

AU - Li, Xiao Feng

AU - Zhou, Quan

AU - Xing, Lianping

AU - Cheng, Shao Dan

AU - Ding, Dao Fang

AU - Xu, Le Qin

AU - Tang, De Zhi

AU - Bian, Qin

AU - Xi, Zhi Jie

AU - Zhou, Chongjian

AU - Shi, Qi

AU - Wang, Yong Jun

N1 - Funding Information: This work was supported by the National Science Fund for Distinguished Young Scholars ( 30625043 ), the International Cooperation Programs of National Natural Science Foundation of China ( 30710103904 ), National Basic Research Program of China (973 Program 2010CB530400 ), the International Technical Cooperation Key Project Plan, Chinese Science and Technology Committee Emphasis ( 2006DFA32670 ), the Project of National Natural Science Foundation of China ( 30930111 , 30973760 , 30901914 , 30600829 , 30701118 and 30572398 ), Changjiang Scholar Chair Professor project (Teach people (2009) 17), Shanghai Medical leading talent support scheme ( LJ06018 ), Shanghai Education Innovation Project ( 08YZ56 ), The basic key project of Shanghai Science and Technology Commission ( 07JC14050 ), Shanghai Youth Science and Technology Development plan project ( 07QA14051 , 09QA1405600 ), Shanghai University Innovation Team Programme (Shanghai Education Commission, Division 6 (2009)), The Ministry of Education Doctoral Fund ( 20070268004 ), Modernization of Chinese medicine-Shanghai Science and Technology Commission special ( 09dZ1977200 ), Shanghai University Select and Train Outstanding Young Teachers in Special Fund ( szy09021 ), Natural Science Foundation of Shanghai ( 11ZR1437100 ), National Institutes of Health PHS awards ( AR48697 to LX).

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

KW - Cartilage endplate

KW - Intervertebral disc

KW - Intervertebral disc degeneration

KW - Osteoclast

KW - Osteoprotegerin

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DO - 10.1016/j.bone.2011.03.773

M3 - Article

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SN - 8756-3282

VL - 48

SP - 1362

EP - 1369

JO - Bone

JF - Bone

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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