Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis

Background Lumbar spinal stenosis (LSS) is a common cause of low back pain with degenerative spinal change in older adults. Telomeres are repetitive nucleoprotein DNA sequences of TTAGGG at the ends of chromosomes. Oxidative stress originates from an imbalance in pro-oxidant and antioxidant homeostasis that results in the production of reactive oxygen species (ROS). The purpose of this study was to investigate relative telomere length (RTL) and oxidative DNA damage in ligamentum flavum (LF) tissue from LSS patients. Methods Forty-eight patients with LSS participated in this study. Genomic DNA from non-hypertrophic and hypertrophic LF tissue were analyzed by real-time polymerase chain reaction for relative telomere length (RTL). 8-hydroxy 2′-deoxygaunosine (8-OHdG) levels were determined by using enzyme-linked immunosorbent assay. We cultivated LF fibroblast cells from patients in different ages (61, 66, and 77 years). After each cultivation cycle, we examined RTL and senescence-associated β-galactosidase (SA-β-gal) expression. Results The hypertrophic LF had significantly lower RTL than non-hypertrophic LF (P = 0.04). The levels of 8-OHdG were significantly higher in hypertrophic LF compared to non-hypertrophic LF (P = 0.02). With advancing cell culture passage, the number of cells in each passage was significantly lower in hypertrophic LF fibroblast cells than non-hypertrophic LF fibroblast cells. When evaluated with SA-β-gal staining, all senescent LF fibroblast cells were observed at earlier passages in hypertrophic LF compared with non-hypertrophic LF fibroblast cells. Discussion Our results showed that patients with LSS displayed an accelerated RTL shortening and high oxidative stress in hypertrophic LF. These findings implied that telomere shortening and oxidative stress may play roles in the pathogenesis of hypertrophic LF in lumbar spinal stenosis

Vitamin D Inadequacy Affects Skeletal Muscle Index and Physical Performance in Lumbar Disc Degeneration

Lumbar disc degeneration (LDD) is one of the fundamental causes of low back pain. The aims of this study were to determine serum 25-hydroxyvitamin D (25(OH)D) levels and physical performance and to investigate the relationship between serum vitamin D levels, muscle strength and physical activity in elderly patients with LDD. The participants were 200 LDD patients, including 155 females and 45 males aged 60 years and over. Data on body mass index and body composition were collected. Serum 25(OH)D and parathyroid hormone levels were measured. Serum 25(OH)D was classified into the insufficiency group: <30 ng/mL and the sufficiency group: ≥30 ng/mL. Muscle strength was assessed by grip strength, and physical performance (short physical performance battery) was evaluated by the balance test, chair stand test, gait speed, and Timed Up and Go (TUG) test. Serum 25(OH)D levels in LDD patients with vitamin D insufficiency were significantly lower than in those with vitamin D sufficiency (p < 0.0001). LDD patients with vitamin D insufficiency had a prolonged time in physical performance on gait speed (p = 0.008), chair stand test (p = 0.013), and TUG test (p = 0.014) compared to those with vitamin D sufficiency. Additionally, we found that serum 25(OH)D levels were significantly correlated with gait speed (r = −0.153, p = 0.03) and TUG test (r = −0.168, p = 0.017) in LDD patients. No significant associations with serum 25(OH)D status were observed for grip strength and balance tests among patients. These findings demonstrate that higher serum 25(OH)D levels are associated with better physical performance in LDD patients

Vitamin D Inadequacy Affects Skeletal Muscle Index and Physical Performance in Lumbar Disc Degeneration

Lumbar disc degeneration (LDD) is one of the fundamental causes of low back pain. The aims of this study were to determine serum 25-hydroxyvitamin D (25(OH)D) levels and physical performance and to investigate the relationship between serum vitamin D levels, muscle strength and physical activity in elderly patients with LDD. The participants were 200 LDD patients, including 155 females and 45 males aged 60 years and over. Data on body mass index and body composition were collected. Serum 25(OH)D and parathyroid hormone levels were measured. Serum 25(OH)D was classified into the insufficiency group: p p = 0.008), chair stand test (p = 0.013), and TUG test (p = 0.014) compared to those with vitamin D sufficiency. Additionally, we found that serum 25(OH)D levels were significantly correlated with gait speed (r = −0.153, p = 0.03) and TUG test (r = −0.168, p = 0.017) in LDD patients. No significant associations with serum 25(OH)D status were observed for grip strength and balance tests among patients. These findings demonstrate that higher serum 25(OH)D levels are associated with better physical performance in LDD patients

Telomere Shortening and Increased Oxidative Stress in Lumbar Disc Degeneration

Lumbar disc degeneration (LDD) contributes to low back pain. This study aimed to determine relative telomere length (RTL), oxidative stress status, and antioxidant levels and examine the relationships between RTL, oxidative stress, and the severity in LDD patients. A total of 100 subjects, 50 LDD patients and 50 healthy controls, were enrolled in the case–control study. Blood leukocyte RTL was analyzed using quantitative real-time polymerase chain reaction. Lipid peroxidation was determined by malondialdehyde (MDA) assay. Plasma 8-hydroxy 2′-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay. Total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) in plasma were also measured. The LDD patients had significantly shorter telomeres than the healthy controls (p = 0.04). Blood leukocyte RTL was inversely correlated with the LDD severity (r = −0.41, p = 0.005). Additionally, plasma MDA and 8-OHdG levels were markedly greater in LDD patients than in the controls (p = 0.01 and p = 0.002, respectively). Furthermore, the plasma MDA level showed a positive correlation with the radiographic severity (r = 0.49, p = 0.001). There was a positive correlation between plasma 8-OHdG and the severity (r = 0.60, p < 0.001). Moreover, plasma TAC and FRAP levels were significantly lower in LDD patients than in the controls (p = 0.04). No significant differences in plasma TAC and FRAP were observed among the three groups of LDD severity. We found that RTL was negatively correlated with the severity while plasma MDA and 8-OHdG levels were positively correlated with the severity. These findings suggest that blood leukocyte RTL, plasma MDA, and 8-OHdG may have potential as noninvasive biomarkers for the assessment of severity in LDD

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient’s quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1β were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery