Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats.

Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.

Vitamin D/VDR in the pathogenesis of intervertebral disc degeneration: Does autophagy play a role?

To date, the underlying mechanisms involved intervertebral disc degeneration (IDD) remain unclear, which has hindered the development of molecular biological therapy for IDD. Autophagy is vital for intracellular quality control and metabolic balance in intervertebral disc cells. Hence, autophagy homeostasis is important. Emerging evidence has implicated vitamin D (VD) and the vitamin D receptor (VDR) in IDD progression because of their effects on different autophagy steps. However, the results of clinical trials in which VD supplementation was assessed as a treatment for IDD are controversial. Furthermore, experimental studies on the interplay between VD/VDR and autophagy are still in their infancy. In view of the significance of the crosstalk between VD/VDR and autophagy components, this review focuses on the latest research on VD/VDR modulation in autophagy and investigates the possible regulatory mechanisms. This article will deepen our understanding of the relationship between VD/VDR and autophagy and suggests novel strategies for IDD prevention and treatment.

[Research advances in prevention and treatment of intervertebral disc degeneration by targeting mitochondrial quality control].

Intervertebral disc degeneration(IDD) is a common clinical degenerative disease of the musculoskeletal system, which increases the risk of lower back pain, severely reduces patients' quality of life and work efficiency, and imposes a large economic burden on society. Mitochondria, as the "power stations" of eukaryotic cells, are involved in many key biological processes, and their abnormal function can induce cellular dysfunction and lead to the development of a series of degenerative diseases. Recent studies have revealed that mitochondrial quality control(MQC) imbalance, characterized by abnormalities in mitochondrial oxidative stress, kinetics, mitophagy and biogenesis, plays an important role in IDD. The research reviewed the progress of the role of MQC in IDD and summarized traditional Chinese medicine monomers and small molecule compounds targeting MQC for the treatment of IDD, with the aim of providing reference and new ideas for studying novel therapeutic strategies for IDD.

Curcumol Alleviates the Inflammation of Nucleus Pulposus Cells via the PI3K/Akt/NF-κB Signaling Pathway and Delays Intervertebral Disk Degeneration.

BACKGROUND: Intervertebral disk degeneration (IVDD) is closely associated with inflammatory environments. Curcumol has been shown to alleviate inflammation in various disease models, but its effects on IVDD remain unclear. In this study, we sought to determine the mechanism of curcumol in tumor necrosis factor (TNF)-α-induced nucleus pulposus cells and a mouse IVDD model. METHODS: Nucleus pulposus cells were pretreated with curcumol and then exposed to TNF-α. Cell viability was analyzed using CCK-8, and the messenger ribonucleic acid and protein levels of inflammatory cytokines and PI3K/Akt/NF-κB-related signaling molecules were detected using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The mouse IVDD model was established by puncturing the C6/7 level of the caudal spine, and then it was treated with curcumol after surgery. Alcian blue/orange G staining was performed to evaluate the severity of intervertebral disk damage, and immunohistochemistry was performed to detect the expression of TNF-α. Toxicologic effects of curcumol were measured by performing hematoxylin-eosin staining and enzyme-linked immunosorbent assay. RESULTS: Curcumol reduced IL-1ß, IL-6, and TNF-α production in NPCs, and the phosphorylation of proteins in the PI3K/Akt/NF-κB signaling pathway was also decreased. The PI3K/Akt/NF-κB-related signaling molecules decreased when TNF-α-induced NPCs were treated with a PI3K inhibitor; however, curcumol did not reverse these effects. In vivo, curcumol ameliorated the progression of IVDD at the early stage and did not exert toxicologic effects. CONCLUSIONS: These results suggest a potential therapeutic use of curcumol to alleviate inflammation via the PI3K/Akt/NF-κB signaling pathway and delay the progression of IVDD.

Tea Polyphenol Attenuates Oxidative Stress-Induced Degeneration of Intervertebral Discs by Regulating the Keap1/Nrf2/ARE Pathway.

OBJECTIVE: Intervertebral disc degeneration (IDD) and low back pain caused by IDD have attracted public attention owing to their extremely high incidence and disability rate. Oxidative stress is a major cause of IDD. Tea polyphenols (TP) are natural-derived antioxidants extracted from tea leaves. This study explored the protective role of TP on the nucleus pulposus cells (NPCs) of intervertebral discs and their underlying mechanism. METHODS: An in vitro model of H2O2-induced degeneration of NPCs was established. RT-qPCR and western blotting were used to detect the mRNA and protein expression of the targets. An in vivo model of IDD was established via acupuncture of the intervertebral disc. Radiological imaging and histological staining were performed to evaluate the protective role of TP. RESULTS: H2O2 contributed to NPC degeneration by inducing high levels of oxidative stress. TP treatment effectively increased the expression of nucleus pulposus matrix-associated genes and reduced the expression of degeneration factors. Further mechanistic studies showed that TP delayed H2O2-mediated NPC degeneration by activating the Keap1/Nrf2/ARE pathway. In vivo experiments showed that TP delayed the degeneration of NPCs in rats through the Keap1/Nrf2/ARE pathway. CONCLUSION: Our study confirmed that TP activates the Keap1/Nrf2/ARE pathway to exert an antioxidative stress role, ultimately delaying the degeneration of intervertebral discs.

Effect of Tai Chi Chuan on degeneration of lumbar vertebrae and lumbar discs in middle-aged and aged people: a cross-sectional study based on magnetic resonance images.

Objective Exercise has a positive effect on physical fitness. Tai Chi Chuan is a traditional Chinese aerobic exercise. We assessed the effect of Tai Chi on the degeneration of lumbar vertebrae and lumbar discs with magnetic resonance images. Methods This retrospective cohort study involved 2 groups of participants: 27 Tai Chi practitioners with more than 4 years of experience with regular Tai Chi exercise and 24 sex- and age-matched participants without Tai Chi experience. The lumbar magnetic resonance images of all participants were collected. The numbers of degenerated lumbar vertebrae and lumbar discs were evaluated by the same radiologist, who was blind to the grouping. Results The Tai Chi practitioners had significantly fewer degenerated lumbar vertebrae (1.9) and lumbar discs (2.3) than the control group (2.6 and 2.9, respectively). The most severely affected lumbar vertebrae and discs were L5 and L4/L5, respectively. Conclusion Regular performance of the simplified Tai Chi 24 form could possibly retard the degeneration of lumbar vertebrae and lumbar discs in middle-aged and aged people.

[Preliminary study of intervention in effect of Bushen Huoxue recipe on calcification of lumbar vertebra cartilage endplate of the aging gerbils].

OBJECTIVE: To study the effect of Bushen Huoxue decoction on calcification of cartilage endplate in lumbar vertebrae. METHODS: Six healthy male gerbils with 2-month-old were selected as normal control group, and 24 7-month-old healthy male gerbils were fed to 12-month-old to establish the aged gerbil model. Thirty gerbils were randomly divided into five groups as follow: the normal control group (n=6), model group (n=6, normal saline 4 ml/kg, intragastric 30 d), Bushen Huoxue low dose group(n=6, 1.9× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue middle dose group(n=6, 3.8× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue high dose group(n=6, 7.6× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), the intervention group administered for 1.36 g from 7-month-old age, 30 d. The animals were sacrificed at the age of 2 months in the normal control group and 12 months of age in the other groups. The morphology of the lumbar vertebral cartilage endplate, the area of vascular bud, the ratio of non-calcified/calcified layer were analysis by HE chromosome visual method. The expression of type X collagen and BMPs in cartilage endplates were detected by rabbit monoclonal immunohistochemical staining. RESULTS: The relative area of the vascular buds cartilage endplate measurements showed that compared with the model group, middle dose group and normal control group increased (P<0.05), high and low dose groups all had different degrees of increase, but no statistical significance(P>0.05). The ratio of cartilage endplate thickness of non-calcified/calcified showed that compared with the model group, Bushen Huoxue middle dose, normal control group increased, with statistical significance(P<0.05), and high and low dose groups all had different degrees of increase, but there were no statistical significance(P>0.05). Compared with the model group, the expression of type X collagen in the cartilage endplate of the normal group, the Bushen Huoxue low, middle and high dose groups decreased, and had statistical significance(P<0.01); compared with the model group, the expression of BMPs in the normal group, Bushen Huoxue middle dose group increased, with statistically significant(P<0.01), while the high and low dose groups increased in different degrees, but there was no statistical significance(P>0.05). CONCLUSIONS: Bushen Huoxue prescription can delay the calcification of cartilage endplate in the process of aging, suggesting that it can be used as a preventive medicine for early disc degeneration.

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

UNLABELLED: We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae. INTRODUCTION: The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats. METHODS: We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression. RESULTS: At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats. CONCLUSIONS: Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.

Inhibitory effects of platelet-rich plasma on intervertebral disc degeneration: a preclinical study in a rabbit model.

BACKGROUND: Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. This study aimed to assess the effects of PRP in a rabbit model of IDD (annulus fibrosus puncture). MATERIAL/METHODS: Thirty-six adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C) (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6 IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin and eosin, Masson's trichrome, and Safranin O staining, and type II collagen immunohistochemistry. RESULTS: Over time, IVD height and disc imaging signal intensity decreased gradually in groups B and C, but only slightly in group A (baseline: 100% for all groups; A: 95.9±4.2% at 4 weeks, 90.1±8.4 at 6 weeks; B: 75.3±5.7% at 4 weeks, 70.8±6.4% at 6 weeks; C: 74.7±5.5% at 4 weeks, 69.9±6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative histological changes in IVDs in groups B and C were more severe compared with group A. CONCLUSIONS: Platelet-rich plasma interventions can effectively attenuate the IDD process in rabbits.

Calcium pentosan polysulfate and sodium pentosan polysulfate may be used to treat intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a major health problem world-wide, and several spinal disorders are closely associated with it. Although people have invested a great deal of time and effort, how to prevent and reverse the IDD for the researchers is still a difficult and hot issue. Intervertebral disc belongs to cartilage tissue, and IDD also is the cartilage degeneration disease. A large quantity of studies have shown that Calcium pentosan polysulfate (CaPPS) and sodium pentosan polysulfate (NaPPS) possess chondroprotective activities and play an important role in maintaining cartilage integrity. We reasonably hypothesize that NaPPS and CaPPS may be used to treat IDD. The possible mechanism may include that: (1) the significant effects of NaPPS and CaPPS in improving capillary blood flow could maintain nutritional supply to intervertebral disc, and preserve intervertebral disc tissue against degeneration; (2) CaPPS and NaPPS preserve cartilage integrity, proteoglycan synthesis, and improve cartilage biomechanical properties; (3) as the multifaceted exosite inhibitors of proteinases NaPPS and CaPPS strongly impede the activity and production of proteinases; (4) promotion of the balance between proteinases and TIMPs also may be involved in treating IDD; (5) NaPPS and CaPPS exhibit potent anti-inflammatory effects, and then reduce inflammation-induced IDD. If the hypothesis were conformed, the symptoms caused by IDD and its related diseases would be a corresponding alleviation or even disappearance, which could greatly alleviate the suffering of patients from disc degeneration diseases. Certainly, many roles of CaPPS and NaPPS, such as effectiveness, safety and side effects, need to be tested, and further works such as animal model and clinical trial, need to be done to prove this hypothesis.