17β-Estradiol/extrogen receptor β alleviates apoptosis and enhances matrix biosynthesis of nucleus pulposus cells through regulating oxidative damage under a high glucose condition

Yang, Di; Zhu, Danjie; Zhu, Shaoyu; Feng, Fabo; Chen, Gong; Chen, Chunmao; Chen, Liang

doi:10.1016/j.biopha.2018.08.084

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…Although the effects of sex hormones on the metabolism of IVD cells was first identified in 1969 59 it is only in the last decade that these have been shown to significantly impact on degenerative processes in the IVD. 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 In order to avoid biological spread and cyclical variation in data that would complicate data analysis and development of a prospective IVDD model, female animals may be examined in a separate data set from male data to ensure any pathophysiological sexual dimorphism is identified. Ideally this would include both actively cycling and “post‐menopausal” (likely gonadectomized) female cohorts to include study of the cyclical fluctuations in circulating female sex hormone levels.…”

Section: The Involvement Of Sex Hormones In Ivd Pathobiologymentioning

confidence: 99%

Intervertebral disc degeneration and how it leads to low back pain

Diwan

Melrose

2022

JOR Spine

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The purpose of this review was to evaluate data generated by animal models of intervertebral disc (IVD) degeneration published in the last decade and show how this has made invaluable contributions to the identification of molecular events occurring in and contributing to pain generation. IVD degeneration and associated spinal pain is a complex multifactorial process, its complexity poses difficulties in the selection of the most appropriate therapeutic target to focus on of many potential candidates in the formulation of strategies to alleviate pain perception and to effect disc repair and regeneration and the prevention of associated neuropathic and nociceptive pain. Nerve ingrowth and increased numbers of nociceptors and mechanoreceptors in the degenerate IVD are mechanically stimulated in the biomechanically incompetent abnormally loaded degenerate IVD leading to increased generation of low back pain. Maintenance of a healthy IVD is, thus, an important preventative measure that warrants further investigation to preclude the generation of low back pain. Recent studies with growth and differentiation factor 6 in IVD puncture and multi‐level IVD degeneration models and a rat xenograft radiculopathy pain model have shown it has considerable potential in the prevention of further deterioration in degenerate IVDs, has regenerative properties that promote recovery of normal IVD architectural functional organization and inhibits the generation of inflammatory mediators that lead to disc degeneration and the generation of low back pain. Human clinical trials are warranted and eagerly anticipated with this compound to assess its efficacy in the treatment of IVD degeneration and the prevention of the generation of low back pain.

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Section: The Involvement Of Sex Hormones In Ivd Pathobiologymentioning

confidence: 99%

Intervertebral disc degeneration and how it leads to low back pain

Diwan

Melrose

2022

JOR Spine

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“…Although the effects of sex hormones on the metabolism of IVD cells was first identified in 1969 44 it is only in the last decade that these have been shown to significantly impact on degenerative processes in the IVD. 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 It is therefore critical that both male and female animals be examined and data collected and separately analyzed to ensure any pathophysiological sexual dimorphism is identified. Ideally this would include both actively cycling and “post‐menopausal” (likely gonadectomized) female cohorts to mimic and model clinically relevant human populations.…”

Section: The Involvement Of Sex Hormones In Intervertebral Disc Patho...mentioning

confidence: 99%

“…An aspect that has emerged in the last decade relevant to the development of prospective animal models of IVDD is the role that sex hormones may have. Although the effects of sex hormones on the metabolism of IVD cells was first identified in 1969 44 it is only in the last decade that these have been shown to significantly impact on degenerative processes in the IVD 44–62 . It is therefore critical that both male and female animals be examined and data collected and separately analyzed to ensure any pathophysiological sexual dimorphism is identified.…”

Section: The Involvement Of Sex Hormones In Intervertebral Disc Patho...mentioning

confidence: 99%

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

et al. 2023

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Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama/alpaca, horse and kangaroo have emerged as new large species for IVD studies, and only time will tell if they will surpass the utility of existing models. The complexity of IVD degeneration poses difficulties in the selection of the most appropriate molecular target of many potential candidates, to focus on in the formulation of strategies to effect disc repair and regeneration. It may well be that many therapeutic objectives should be targeted simultaneously to effect a favorable outcome in human IVD degeneration. Use of animal models in isolation will not allow resolution of this complex issue and a paradigm shift and adoption of new methodologies is required to provide the next step forward in the determination of an effective repairative strategy for the IVD. AI has improved the accuracy and assessment of spinal imaging supporting clinical diagnostics and research efforts to better understand IVD degeneration and its treatment. Implementation of AI in the evaluation of histology data has improved the usefulness of a popular murine IVD model and could also be used in an ovine histopathological grading scheme that has been used to quantify degenerative IVD changes and stem cell mediated regeneration. These models are also attractive candidates for the evaluation of novel anti‐oxidant compounds that counter inflammatory conditions in degenerate IVDs and promote IVD regeneration. Some of these compounds also have pain‐relieving properties. AI has facilitated development of facial recognition pain assessment in animal IVD models offering the possibility of correlating the potential pain alleviating properties of some of these compounds with IVD regeneration.

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“…A few recent reports have indicated that the DM may engender IVDD [6,7], by inducing degenerative changes such as apoptosis, senescence and matrix degradation of nucleus pulposus (NP) cells [8]. These evidences imply that the suppression of high glucose might be a potential strategy for delaying disc degeneration in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Platelet-Derived Biomaterials Exert Chondroprotective and Chondroregenerative Effects on Diabetes Mellitus-Induced Intervertebral Disc Degeneration

Chang

Chan

et al. 2021

Life

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Complications of diabetes mellitus (DM) range from acute to chronic conditions, leading to multiorgan disorders such as nephropathy, retinopathy, and neuropathy. However, little is known about the influence of DM on intervertebral disc degeneration (IVDD). Moreover, traditional surgical outcomes in DM patients have been found poor, and to date, no definitive alternative treatment exists for DM-induced IVDD. Recently, among various novel approaches in regenerative medicine, the concentrated platelet-derived biomaterials (PDB), which is comprised of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), etc., have been reported as safe, biocompatible, and efficacious alternatives for various disorders. Therefore, we initially investigated the correlations between DM and IVDD, through establishing in vitro and in vivo DM models, and further evaluated the therapeutic effects of PDB in this comorbid pathology. In vitro model was established by culturing immortalized human nucleus pulposus cells (ihNPs) in high-glucose medium, whereas in vivo DM model was developed by administering streptozotocin, nicotinamide and high-fat diet to the mice. Our results revealed that DM deteriorates both ihNPs and IVD tissues, by elevating reactive oxygen species (ROS)-induced oxidative stress, inhibiting chondrogenic markers and disc height. Contrarily, PDB ameliorated IVDD by restoring cellular growth, chondrogenic markers and disc height, possibly through suppressing ROS levels. These data imply that PDB may serve as a potential chondroprotective and chondroregenerative candidate for DM-induced IVDD.

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17β-Estradiol/extrogen receptor β alleviates apoptosis and enhances matrix biosynthesis of nucleus pulposus cells through regulating oxidative damage under a high glucose condition

Cited by 12 publications

References 40 publications

Intervertebral disc degeneration and how it leads to low back pain

Intervertebral disc degeneration and how it leads to low back pain

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

Platelet-Derived Biomaterials Exert Chondroprotective and Chondroregenerative Effects on Diabetes Mellitus-Induced Intervertebral Disc Degeneration

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