Exosomal MATN3 of Urine-Derived Stem Cells Ameliorates Intervertebral Disc Degeneration by Antisenescence Effects and Promotes NPC Proliferation and ECM Synthesis by Activating TGF-ß.

OBJECTIVE: Low back pain (LBP) is one of the top three causes of disability in developed countries, and intervertebral disc degeneration (IDD) is a major contributor to LBP. In the process of IDD, there is a gradual decrease in nucleus pulposus cells (NPCs) and extracellular matrix (ECM). Exosomes are important exocrine mediators of stem cells that can act directly on cells for tissue repair and regeneration. In this study, we determined the antisenescence, cell proliferation promotion, and ECM modulation effects of human urine-derived stem cell (USC) exosomes (USC-exos) on degenerated intervertebral discs and explored the underlying mechanism. METHODS AND MATERIALS: USCs were identified by multipotent differentiation and flow cytometry for mesenchymal stem cell- (MSC-) specific surface protein markers. USC-exos were isolated from the conditioned medium of USCs by ultracentrifugation and then analyzed by transmission electron microscopy (TEM), particle size analysis, and western blotting (WB) for exosome marker proteins. The effects of USC-exos on NPC proliferation and ECM synthesis were assessed by Cell Counting Kit-8 (CCK-8), WB, and immunofluorescence (IF) analyses. The protein differences between normal and degenerative intervertebral discs were mined, and the temporal and spatial variations in matrilin-3 (MATN3) content were determined by WB and IF in the intervertebral disc tissues. The candidate molecules that mediated the function of USC-exos were screened out and confirmed by multiple assays. Meanwhile, the mechanism underlying the candidate protein in USC-exos-induced cell proliferation and regulation of ECM synthesis promoting the activities of NPCs was explored. In addition, the effects of USC-exos on ameliorating intervertebral disc degeneration (IVD) in mice were examined by assessing computed tomography (CT), magnetic resonance imaging (MRI), and histological analyses. RESULTS: The flow cytometry results showed that USCs were positive for CD29, CD44, and CD73, which are USC surface-specific markers, but negative for CD34 and CD45. In addition, USCs showed osteogenic, adipogenic, and chondrogenic differentiation potential. USC-exos exhibited a cup-shaped morphology, with a mean diameter of 49.7 ± 7.3 nm, and were positive for CD63 and TSG101 and negative for calnexin. USC-exos could promote NPC proliferation and ECM synthesis. The protein content of the matrilin family was significantly reduced in degenerative intervertebral discs, and the decrease in MATN3 was the most significant. USC-exos were found to be rich in MATN3 protein, and exosomal MATN3 was required for USC-exos-induced promotion of NPC proliferation and ECM synthesis, as well as alleviation of intervertebral disc degeneration in IVD rats. In addition, the effects of MATN3 in USC-exos were demonstrated to be achieved by activating TGF-ß, which elevated the phosphorylation level of SMAD and AKT. CONCLUSIONS: Our study suggests that reduced MATN3 can be considered a characteristic of intervertebral disc degeneration. USC-exos may represent a potentially effective agent for alleviating intervertebral disc degeneration by promoting NPC proliferation and ECM synthesis by transferring the MATN3 protein.

Analysis of pain symptoms, flexibility and hydroxyproline concentration in individuals with low back pain submitted to Global Postural Re-education and stretching.

Aim: To evaluate pain, flexibility and hydroxyproline (HP) urinary levels in patients with nonspecific low back pain submitted to Global Postural Re-education (GPR) and stretching. Materials & methods: 39 individuals who reported low back pain were randomly assigned to a group submitted to GPR (GPRG) or stretching exercises (SG) for 8 weeks. Pain and flexibility were assessed using the Borg CR10 scale and goniometry, respectively. Results: The GPR group showed a significant reduction in the HP levels and significant improvements in flexibility after the intervention when compared with SG. Both groups presented a significant reduction in HP and pain after the intervention. Conclusion: Both interventions were effective in the treatment of low back pain. However, the GPR method presented better responses than stretching.

The smallest worthwhile effect of primary care physiotherapy did not differ across musculoskeletal pain sites.

OBJECTIVES: To determine and compare estimates of the smallest worthwhile effect (SWE) for physiotherapy in neck, shoulder, and low-back pain patients and to investigate the influence of sociodemographic, clinical, and psychological factors on these estimates. METHODS: A structured telephone interview was conducted before treatment was commenced in 160 patients referred for primary care physiotherapy. The benefit-harm trade-off method was used to estimate the SWE of physiotherapy for the following outcomes; pain, disability, and time to recovery, compared with the improvement achieved without any treatment (natural course). Regression analyses were used to assess the influence of sociodemographics, clinical variables, and intake scores on pain, disability, and psychological scales. RESULTS: The median SWE for improvements on pain and disability was 20% (interquartile range 10%-30%), and the SWE for time to recovery was 10 days (interquartile range 7-14 days) over a period of 6 weeks. These estimates did not differ with respect to pain location (neck, shoulder, or back) and were generally unaffected by sociodemographic, clinical, and psychological factors. CONCLUSION: People with neck, shoulder, and low-back pain need to see at least 20% of additional improvement on pain and disability compared with natural recovery to consider that the effect of physiotherapy is worthwhile, given its costs, potential side effects, and inconveniences.

Time control, catecholamines and back pain among young nurses.

OBJECTIVES: This study had two objectives. First, it addressed concern with the contribution of work stressors and resources to the development of back pain, over and above the influence of biomechanical work factors. Second, using recent models about the role of the sympathetic-adrenal medullar system in musculoskeletal problems as its basis, it tested whether low-back pain is associated with higher levels of catecholamines. METHODS: Altogether 114 nurses filled out a questionnaire in their first year of practice and again one year later. In addition, in a subsample of 24 nurses studied intensively at follow-up, urinary catecholamines were assessed at noon, before the end of work, in the evening, and at corresponding times on a day off. Daily stressful experiences and daily mood were also recorded. RESULTS: With control for baseline pain, biomechanical workload, and other potentially confounding variables, time control at the beginning of the study predicted low-back pain a year later. In the subsample, the epinephrine and norepinephrine levels were higher in those reporting more frequent episodes of back pain, the largest differences occurring at the end of work. In addition, control over stressful events at work was lower in this group. CONCLUSIONS: Time control is a risk factor for low-back pain among nurses beyond the influence of physical work load. Low control at work may increase the activity of the sympathetic-adrenal medullar system, which seems to play an important role in the development of musculoskeletal pain.