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Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model

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Abstract

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

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Abbreviations

IVDD:

Intervertebral disc degeneration

CON:

Control

OVX:

Ovariectomy

INS:

Instability

COM:

Combination

TRAP:

Tartrate-resistant acid phosphatase

OSX:

Osterix

Col:

Collagen

VEGF:

Vascular endothelial growth factor

EP:

Endplate

AF:

Annulus fibrosus

NP:

Nucleus pulposus

CT:

Computed tomography

ROI:

Region of interest

BV/TV:

Percent bone volume

BS/TV:

Bone surface density

Tb.N:

Trabecular number

Tb.Th:

Trabecular thickness

Tb.Sp:

Trabecular separation

SMI:

Structural model index

BMDtv:

Total volume bone mineral density

IVD:

Intervertebral disc

SB:

Subchondral bone

Cr:

Cranial

Ca:

Caudal

AOD:

Average optical density

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Acknowledgements

We thank Mr. Yang Fan for helping in micro-CT scanning and analyses, The Laboratory Affiliated to Orthopaedics and Traumatology of Chinese Medicine of Linnan Medical Research Center of Guangzhou University of CM for providing the associated experimental facilities, and Animal Center of Guangzhou University of CM for helping in the implementation of animal experiments.

Funding

This work was supported by the National Natural Science Foundation of China [NSFC, Grant Numbers, 81673992, 81804118] and The Education Department of Guangdong Province [Grant Numbers, A1-AFD018191A117].

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    Authors and Affiliations

    1. The Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, No. 111, Dade Road, Yuexiu District, Guangzhou, 510120, People’s Republic of China

      Zhi-feng Xiao, Guo-yi Su, Yu Hou, Shu-dong Chen, Bing-de Zhao & Ding-kun Lin

    2. Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou, 510405, People’s Republic of China

      Zhi-feng Xiao, Guo-yi Su, Yu Hou, Shu-dong Chen, Bing-de Zhao, Jian-bo He, Ji-heng Zhang, Yan-jun Chen & Ding-kun Lin

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    Contributions

    All authors made a substantial contribution to the data analysis and interpretation, drafting of the manuscript and critical revision of the manuscript for important intellectual content. D-k Lin and Z-f Xiao conceived the study and D-k Lin secured the funding; Z-f Xiao, Guo-yi Su and Shu-dong Chen performed experiments; Yu Hou and Bing-de Zhao contributed to data collection and analysis; Zhi-feng Xiao, Jian-bo He, Ji-heng Zhang and Yan-jun Chen drafted the manuscript. All authors gave their final approval of the version to be published.

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    Correspondence to Ding-kun Lin.

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    All experimental procedures were approved by the Ethics Committee of Guangzhou University of Chinese Medicine and implemented according to the guidelines and regulations for use and care of animals.

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    Zhi-feng Xiao and Guo-yi Su have contributed equally to this work.

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    Xiao, Zf., Su, Gy., Hou, Y. et al. Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model. Calcif Tissue Int 106, 401–414 (2020). https://doi.org/10.1007/s00223-019-00644-8

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