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Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice.
Arthritis Res Ther 2018; 20(1):207AR

Abstract

BACKGROUND

Studies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis.

METHODS

Thirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis.

RESULTS

OVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice.

CONCLUSIONS

OVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration.

Authors+Show Affiliations

The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. The Laboratory Affiliated to Orthopaedics and Traumatology of Chinese Medicine of Linnan Medical Research Center of Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China.The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. The Laboratory Affiliated to Orthopaedics and Traumatology of Chinese Medicine of Linnan Medical Research Center of Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China.The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China.The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. The Laboratory Affiliated to Orthopaedics and Traumatology of Chinese Medicine of Linnan Medical Research Center of Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China.The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China.The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China.The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, China. lindingkuntcm@126.com. The Laboratory Affiliated to Orthopaedics and Traumatology of Chinese Medicine of Linnan Medical Research Center of Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China. lindingkuntcm@126.com. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, China. lindingkuntcm@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30201052

Citation

Xiao, Zhi-Feng, et al. "Osteoporosis of the Vertebra and Osteochondral Remodeling of the Endplate Causes Intervertebral Disc Degeneration in Ovariectomized Mice." Arthritis Research & Therapy, vol. 20, no. 1, 2018, p. 207.
Xiao ZF, He JB, Su GY, et al. Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice. Arthritis Res Ther. 2018;20(1):207.
Xiao, Z. F., He, J. B., Su, G. Y., Chen, M. H., Hou, Y., Chen, S. D., & Lin, D. K. (2018). Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice. Arthritis Research & Therapy, 20(1), p. 207. doi:10.1186/s13075-018-1701-1.
Xiao ZF, et al. Osteoporosis of the Vertebra and Osteochondral Remodeling of the Endplate Causes Intervertebral Disc Degeneration in Ovariectomized Mice. Arthritis Res Ther. 2018 09 10;20(1):207. PubMed PMID: 30201052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice. AU - Xiao,Zhi-Feng, AU - He,Jian-Bo, AU - Su,Guo-Yi, AU - Chen,Mei-Hui, AU - Hou,Yu, AU - Chen,Shu-Dong, AU - Lin,Ding-Kun, Y1 - 2018/09/10/ PY - 2018/01/16/received PY - 2018/08/15/accepted PY - 2018/9/12/entrez PY - 2018/9/12/pubmed PY - 2019/7/19/medline KW - Endplate KW - Intervertebral disc degeneration KW - Microcomputed tomography KW - Osteochondral remodeling KW - Osteoporosis KW - Ovariectomy SP - 207 EP - 207 JF - Arthritis research & therapy JO - Arthritis Res. Ther. VL - 20 IS - 1 N2 - BACKGROUND: Studies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis. METHODS: Thirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis. RESULTS: OVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice. CONCLUSIONS: OVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/30201052/Osteoporosis_of_the_vertebra_and_osteochondral_remodeling_of_the_endplate_causes_intervertebral_disc_degeneration_in_ovariectomized_mice_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-018-1701-1 DB - PRIME DP - Unbound Medicine ER -