ascorbic-acid and Intervertebral-Disc-Degeneration

Intervertebral disc degeneration (IVDD) affects human health. Ascorbic acid (AA) deficiency is a major factor that contributes to the development of degenerative disc disease in the elderly. Here, as a novel treatment with promising applications, we demonstrate that AA treatment inhibited senescence and maintained the proliferation of nucleus pulposus (NP) cells during long-term culture. AA-treated NP cells and acupuncture-treated rat models exhibited degenerative resistance during cell passaging and AA increased cell proliferation and decreased time-related senescence. Interestingly, Kyoto Encyclopedia of Genes and Genomes pathway mapping revealed five top enriched pathways and four pathways were associated with the aldehyde dehydrogenase (ALDH) enzyme family, especially proliferation-related ALDH1A3. Collectively, our findings demonstrate that ALDH1A3 expression was increased by AA treatment, which counteracted degeneration in NP cells over time and rejuvenated maintenance of proliferation in NP cells, which has a promising therapeutic implications in IVDD.

Topics: Aged; Animals; Ascorbic Acid; Cell Proliferation; Humans; Intervertebral Disc Degeneration; Nucleus Pulposus; Rats; Regeneration

To explore the effect of Vitamin C (Vit C) on the apoptosis of human nucleus pulposus (NP) cells induced by tumor necrosis factor a (TNF-alpha) and serum deprivation.. The NP cells were isolated from patients undergoing spine corrective operation by collagenase trypsin. The experiment was divided into 3 groups: Vit C group (group A), TNF-alpha group (group B), and serum deprivation group (group C). Group A was reassigned to Al subgroup (basic medium), A2 subgroup (100 pg/mL Vit C), and A3 subgroup (200 pg/mL Vit C). Group B was reassigned to B0 subgroup (control group), Bi subgroup (100 ng/mL TNF-alpha), B2 subgroup (100 microg/mL Vit C+100 ng/mL TNF-alpha), and B3 subgroup (200 microg/mL Vit C+100 ng/mL TNF-alpha). Group C was reassigned to C0 subgroup (Control group), C1 subgroup (2% FBS), C2 subgroup (2% FBS+100 microg/mL Vit C), and C3 subgroup (2% FBS+200 microg/mL Vit C). After application of 100 pg/mL or 200 microg/mL Vit C for 24 hours, NP cells were stimulated by TNF-alpha and serum deprivation, then the apoptosis rate of NP cells was detected by a flow cytometry, and the gene expressions of the extracellular matrix of NP cells (collagen type I, collagen type II, aggrecan, and Sox9) and apoptosis related genes (p53, FAS, and Caspase 3) were detected by real-time fluoroscent quantitative PCR. Results Group A: Vit C could significantly reduce the apoptosis rate and gene expressions of p53, FAS, and Caspase 3 of NP cells in A2 and A3 subgroups when compared with Al subgroup (P<0.05), but there was no significant difference between A2 subgroup and A3 subgroup (P>0.05); Vit C could promote the expressions of the extracellular matrix (collagen type I, collagen type II, aggrecan, and Sox9) of NP cells in a concentration dependent manner (P<0.05). Group B: TNF-alpha significantly increased the apoptosis rate and the gene expressions of p53, FAS, and Caspase 3 in B1 subgroup when compared with B0 subgroup (P<0.05); however, Vit C significantly increased the apoptosis rate and the gene expressions in B2 subgroup, and significantly decreased them in B3 subgroup when compared with B1 subgroup (P<0.05). Group C: 2% FBS significantly increased the apoptosis rate of NP cells and significantly reduced the gene expressions of p53, FAS, and Caspase 3 in C1 subgroup when compared with C0 subgroup (P<0.05); Vit C could significantly reduce the apoptosis rate and gene expressions of p53, FAS, and Caspase 3 in C3 subgroup, but it could significantly increase them in C2 subgroup when compared with C1 subgroup (P<0.05).. Vit C can promote the synthesis and secretion of extracellular matrix of NP cells. 200 microg/mL Vit C may delay the apoptosis induced by TNF-alpha and serum deprivation, indicating the potential therapeutic effect of Vit C on intervertebral disc degeneration.

Topics: Aggrecans; Apoptosis; Ascorbic Acid; Caspase 3; Cell Proliferation; Cells, Cultured; Collagen Type II; Extracellular Matrix Proteins; Gene Expression; Humans; Intervertebral Disc Degeneration; Tissue Culture Techniques; Tumor Necrosis Factor-alpha

The human aging process is often accompanied by significant increases in degenerative spine disease. The pathophysiology of intervertebral disc degeneration has been extensively studied, but the etiology of this aging-related problem remains poorly understood. The elderly often have lower daily vitamin C intakes and circulating ascorbic acid values than younger people because of problems with poor dentition or mobility, and also are more likely to have underlying sub-clinical diseases that can reduce plasma ascorbate concentrations. Ascorbate is essential for collagen production, and vitamin C deficiency will result in defective connective tissue, including reductions in collagen synthesis and structural stability. It is hypothesised that vitamin C deficiencies may be a key contributing factor in the development of degenerative disk disease (DDD) in the elderly. Once degenerative disc disease has begun, the tissue inflammation that accompanies DDD may further increase vitamin C requirements in the affected patient, thereby creating a cascade of positive feedbacks that potentially accelerates and contributes to further disc degeneration and low-back pain. Aggressive monitoring of patient ascorbate status, as well as more finely-calibrated RDAs for vitamin C that explicitly take into account the patient's age, may be required if aging-related degenerative disk disease is to be minimised.

Topics: Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Extracellular Matrix; Humans; Intervertebral Disc Degeneration; Low Back Pain