Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats

Luo, Yunhua; Zhang, Liu; Wang, Wenya; Hu, Qifeng; Song, Huiping; Su, Yanling; Zhang, Yingze

doi:10.1016/j.bone.2013.03.002

Cited by 40 publications

(36 citation statements)

References 63 publications

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“…The present study shows deterioration of lumbar vertebral body bone microstructure in rats at 12 and 24 weeks after OVX. Furthermore, biomechanical testing showed weaker vertebral body trabecular bone at 24 weeks post-OVX, which was similar to our previous study [7,8]. Based on the recognition of wide variation in the degenerative changes in intervertebral disk, the use of a grading system pioneered by Wang et al provides a semiquantitative assessment of the severity of disk degradation in the end plate, nucleus pulposus, and annulus fibrosus [7].…”

Section: Discussionsupporting

confidence: 65%

“…The samples appearing yellow or brownish yellow were considered as positive staining. All sections were semiquantitatively analyzed by Image Pro Plus (IPP) version 6.0 software, and the integrated optical density (IOD) was measured from staining of six fields for each section using one section per rat, on the images at×400 magnification [8,15]. The average IOD from three observers was the final observation result and used for statistical analysis.…”

Section: Immunohistochemistry Analysismentioning

confidence: 99%

“…Relative estrogen deficiency may contribute to accelerated disk degeneration in postmenopausal females [6]. In addition, our previous studies have revealed a strong association between osteopenia and disk degeneration in OVX rats, and intervention by alendronate, a widely accepted antiresorptive agent, could not only prevent osteopenia but also inhibit intervertebral disk degeneration [7,8].…”

Section: Introductionmentioning

confidence: 98%

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Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats

et al. 2015

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Section: Discussionsupporting

confidence: 65%

Section: Immunohistochemistry Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats

et al. 2015

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“…For each image, the thickness was determined by an average of 3 measurements obtained in the cartilage endplate. The ratio of cartilage tissue area to the entire endplate was measured and calculated as previously described [48, 61], and the measurements were assessed by 3 pathologists blinded to the treatments.…”

Section: Methodsmentioning

confidence: 99%

“…Among these cytokines, MIF [5, 37] not only plays a role in CEP degeneration [37-40] but also functions as a positive regulator of proinflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) and thus stimulates adjacent disc tissue degeneration. More importantly, the cartilage canal and vascular buds in the vertebral endplate are specific fine structures [41-43] that can transport drugs to vertebral endplate by systemic administration [44-48], rendering the CEP as an ideal drug target for reducing IVD degeneration. Together, the aforementioned findings collectively suggest that the CEP represents a potential therapeutic target for the treatment of IVD diseases [49, 50].…”

Section: Introductionmentioning

confidence: 99%

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

Wang

Huang

Dong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. Methods: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. Results: In CEP cells, Interleukin (IL)-1β upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1β-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. Conclusion: LY could serve as a potential drug for treating IVD disease.

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Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats

Zhou

Tian

Gou

et al. 2015

Journal of Bone and Mineral Research

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Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1-34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L 4 -L 5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n ¼ 20) (V ¼ vehicle): ShamþV, OVXþV, ShamþPLFþV, OVXþPLFþV, OVXþPLFþPTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia.

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Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats

Cited by 40 publications

References 63 publications

Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats

Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats

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