The importance of psoas muscle on low back pain: a single-center study on lumbar spine MRI.

Background: Low back pain (LBP) is the most frequent indication to magnetic resonance imaging (MRI) examinations of the lumbosacral spine. The individual role of soft tissues, including muscles, on LBP is not fully understood and the contribution of each MRI-derived parameter of soft tissues status on the intensity of LBP has not been investigated in detail. Methods: The study design was observational retrospective, single center carried out at a University Hospital. Images were acquired using a using a 1.5 Tesla scanner. Patients completed a symptom questionnaire and rated their pain intensity using the Visual Analogue Scale (VAS). The VAS scores ​​were categorized as mild, moderate, and severe using cutoff values of 3.8 and 5.7, based on the literature. Biometric data, including weight and height, were also recorded to calculate the body mass index (BMI). The ratios between intramuscular fat infiltration and net muscle area were also calculated. Patient sample included 94 patients with LBP underwent MRI of the lumbosacral spine. Results: The stepwise analysis revealed that increasing psoas net area was associated with lower VAS levels (odds ratio [OR]: 0.94: 95% confidence interval [CI]: 0.90-0.98; p=.005), and an increase of one square centimeter of total psoas area resulted in a greater probability of reporting a mild (+1.21%; 95% CI: 0.37, 2.05%) or a moderate VAS (+0.40%; 95% CI: -0.02, 0.82%), Furthermore, a more severe VAS was associated with a higher BMI (OR: 1.13; 95% CI: 1.00-1.27). Conclusion: Our study demonstrates a relationship between LBP and MRI parameters of paravertebral and psoas muscles status. The psoas muscle is extremely important for spine stabilization and is linked to clinical symptoms of patients affected by LBP. These findings could contribute to future studies and improve treatment options in patients with LBP, possibly reducing the impact on disability, quality of life and socioeconomical burden.

Higher Accuracy and Better Clinical Outcomes in Navigated Thoraco-Lumbar Pedicle Screw Fixation versus Conventional Techniques: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: This study aims to compare pedicle screw accuracy, clinical outcomes, and complications between navigated and conventional techniques. SUMMARY OF BACKGROUND DATA: In the last decades, intraoperative navigation has been introduced in spinal surgery to prevent risks and complications. METHODS: The search was executed on Cochrane Central Library, PubMed and Scopus on 30 April 2023. Randomized controlled trials, prospective and retrospective studies that compared pedicle screw accuracy in the thoracic-lumbar-sacral segments, blood loss, operative time, hospital stay, intraoperative and postoperative revision of screws, neurological and systemic complications, Visual Analogue Scale (VAS), and Oswestry Disability Index (ODI) between navigated and freehand or fluoroscopy-assisted techniques were included in this study. The meta-analysis was performed using Review Manager software. Clinical outcomes were assessed as continuous outcomes with mean difference, while pedicle screw accuracy and complications were assessed as dichotomous outcomes with odds ratio, all with 95% confidence intervals. The statistical significance of the results was fixed at P<0.05. RESULTS: This meta-analysis included 30 studies for a total of 17911 patients and 24600 pedicle screws. Statistically significant results in favour of the navigated technique were observed for accuracy of pedicle screws (P=0.0001), hospital stay (P=0.0002), blood loss (P<0.0001), postoperative revision of pedicle scews (P<0.00001), and systemic complications (P=0.0008). In particular, the positioning of the screws was clinically acceptable in 96.2% of the navigated group, and 94.2% with traditional techniques. No significant differences were found in VAS, ODI, and operative time between the two groups. CONCLUSION: Navigated pedicle screw fixation has been demonstrated to be a safe and effective technique with high improvement in clinical outcomes and accuracy in patients undergoing spinal fusion compared to conventional techniques. LEVEL OF EVIDENCE: III.

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources.

Background: Chronic discogenic low back pain (LBP) poses a significant global burden, yet effective therapeutic interventions directly targeting the underlying degenerative process remain elusive. After demonstrating promising results in preclinical studies, intradiscal injection of cell-based treatments has been increasingly investigated in the clinical setting. However, most clinical trials failed to reach publication, with the few available reports showing only minor improvements. The aim of this study was to analyze the prospective clinical trials registered on ClinicalTrials.gov investigating cell therapies for LBP, with a specific emphasis on identifying critical obstacles hindering study completion, including trial design and funding sources. Methods: A systematic search of prospective clinical trials investigating cell-based treatments for chronic LBP due to intervertebral disc degeneration was performed on ClinicalTrials.gov. Extracted data encompassed study design, recruitment, experimental treatment modalities, investigated outcomes, current status, completion date, publication status, and funding sources. Fisher's exact test assessed associations between categorical variables, while a multiple logistic regression model aimed to identify factors potentially linked to the publication status of the studies. Results: Our search identified 26 clinical trials. Among these, only 7 (26.9%) were published, and none of the other studies marked as completed reported any results on ClinicalTrials.gov. Fifty percent of included trials were funded by universities, whereas the rest was sponsored by industry (38.5%) or private institutions (11.5%). Experimental treatments primarily involved cell-based or cell-derived products of varying sources and concentrations. Products containing carriers, such as hyaluronic acid or fibrin, were more frequently funded by industry and private organizations (p = 0.0112). No significant differences emerged when comparing published and nonpublished studies based on funding, as well as between publication status and other variables. Conclusion: Most clinical trials exploring cell-based disc regenerative therapies for chronic LBP have never reached completion, with only a small fraction reporting preliminary data in publications.

Intraoperative Cone-Beam Computed Tomography Navigation Versus 2-Dimensional Fluoroscopy in Single-Level Lumbar Spinal Fusion: A Comparative Analysis.

OBJECTIVE: Several studies have advocated for the higher accuracy of transpedicular screw placement under cone-beam computed tomography (CBCT) compared to conventional 2-dimensional (2D) fluoroscopy. The superiority of navigation systems in perioperative and postoperative outcomes remains a topic of debate. This study aimed to compare operative time, screw placement time and accuracy, total radiation dose, perioperative and postoperative outcomes in patients who underwent transpedicular screw fixation for degenerative lumbar spondylolisthesis (DLS) using intraoperative CBCT navigation versus 2D fluoroscopy. METHODS: A retrospective analysis was conducted on patients affected by single-level DLS who underwent posterior lumbar instrumentation with transpedicular screw fixation using surgical CBCT navigation (NV group) or 2D fluoroscopy-assisted freehand technique (FH group). Demographics, screw placement time and accuracy, operative time, total radiation dose, intraoperative blood loss, screw revision rate, complications, and length of stay (LOS) were assessed. RESULTS: The study included a total of 30 patients (NV group: n = 15; FH group: n = 15). The mean screw placement time, operative time, and LOS were significantly reduced in the NV group compared to the FH group (p < 0.05). The total radiation dose was significantly higher in the NV group (p < 0.0001). No significant difference was found in terms of blood loss and postoperative complications. CONCLUSION: This study suggests that intraoperative CBCT-navigated single-level lumbar transpedicular screw fixation is superior in terms of mean screw placement time, operative time, and LOS compared to 2D fluoroscopy, despite a higher intraoperative radiation exposure.

Importance of an Integrated Assessment of Functional Disability and Work Ability in Workers Affected by Low Back Pain.

Background: This study examines the relationship between functional disability and work ability in workers affected by low back pain (LBP) through an analysis of correlations between the Oswestry Disability Index (ODI) and Work Ability Index (WAI). The role of personal and work factors on functional disability/work ability levels has also been studied. LBP is the most common musculoskeletal problem and a major disabling health problem worldwide. Its etiology is multifactorial. Multidisciplinary approaches may help reduce the burden of pain and disability and improve job continuity and reintegration at work. Methods: A cohort of 264 patients affected by LBP from an Italian outpatient clinic were included in a clinical diagnostic/therapeutic trial aiming at rehabilitation and return to work through an integrated investigation protocol. Data were collected during the first medical examination using anamnestic and clinical tools. The final sample is composed of 252 patients, 57.1% man, 44.0 % blue collars, 46.4% with the high school degree, 45.6% married. Results: WAI and ODI reported a negative and fair correlation (r = -0.454; p = .000). Workers with acute LBP symptoms have a higher probability of severe disability than those with chronic LBP symptoms. White collars without depressive symptoms reported higher work ability - even in chronic disability conditions-than those with depressive symptoms. Conclusion: The study found that ODI and WAI have a convergent validity and this suggests that the two tools measure capture distinctive aspects of disability related to personal, environmental, and occupational characteristics. The most important and modifiable prognostic factors found for ODI and WAI were depressive symptoms, workday absence, and intensity of back pain. The study also found a mild association between age and ODI. The study's findings highlight the importance of using a multidisciplinary approach to manage and prevent disability due to LBP.

Exploring Borate-Modified Calcium Phosphate Ceramics: Antimicrobial Potential and Cytocompatibility Assessment.

Addressing periprosthetic infections, which present significant healing challenges that often require revision surgeries, necessitates the development of novel antibacterial materials and implants. Current research focuses on creating materials that hinder bacterial adhesion, colonization, and proliferation in surrounding tissues. Boron (B)-containing compounds are known for their antibacterial properties and potential in bone metabolism for regenerative medicine. In this study, we synthesized B-containing tricalcium phosphate (0.3B-TCP) with 1.1 wt.% B content via precipitation from aqueous solutions and sintering at 1100 °C. X-ray diffraction confirmed the ceramic's primary crystalline phase as ß-TCP, with B evenly distributed according to energy-dispersive spectroscopy data. Electron paramagnetic resonance (EPR) data verified stable paramagnetic borate anions, indicating successful BO33- substitution for phosphate groups. The microstructural properties of 0.3B-TCP ceramic were assessed before and after soaking in a saline solution. Its bending strength was approximately 30 MPa, and its porosity was about 33%. 0.3B-TCP ceramic demonstrated significant antimicrobial efficacy against various bacterial strains and a fungus. Cytotoxicity evaluation using equine adipose tissue-derived mesenchymal stem cells and osteogenic differentiation assessment were conducted. The combination of antibacterial efficacy and good cytocompatibility suggests 0.3B-TCP ceramic as a promising bone substitute material.

Anterior Cruciate Ligament Repair Augmented With Dynamic Intraligamentary Stabilization Is Equivalent to Hamstring Autograft Reconstruction at Short- and Mid-Term Follow-Up: A Systematic Review.

PURPOSE: To compare clinical outcomes, knee stability and complications, failure, and revision rates after anterior cruciate ligament repair (ACLr) with dynamic intraligamentary stabilization (DIS) versus anterior cruciate ligament reconstruction (ACLR) with hamstring autograft for primary ACL ruptures at short and mid-term follow-up. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of PubMed/MEDLINE and Scopus was performed. Studies that evaluated patients undergoing ACLr with DIS or ACLR with hamstring autograft were considered for inclusion. Studies were excluded if patients were affected by concomitant meniscal, ligamentous, or chondral injuries needing surgical treatment, because of their potential confounding effect on postoperative outcomes. The Risk of Bias-2 tool was used to assess the risk of bias in the included studies. The quality of available evidence was rated according to Grading of Recommendations Assessment, Development, and Evaluation recommendations. The study protocol was registered in the PROSPERO database (ID: CRD42023394558). RESULTS: Five randomized controlled trials comparing the outcomes of ACLr with DIS versus ACLR with hamstring autograft met the inclusion criteria. No major differences in terms of patient-reported outcomes (International Knee Documentation Committee subjective form, Lysholm score, Tegner activity scale, Knee injury and Osteoarthritis Outcome Score, visual analog scale satisfaction) or rates of complications, revisions, and failures were found in included studies at all time points. Repair showed greater International Knee Documentation Committee subjective form scores at 5 years in one study, whereas ACLR displayed significantly increased knee stability at 6 months and 5 years in 2 different studies, although the clinical relevance of these differences is doubtful. CONCLUSIONS: The results of this study suggest that ACLr with DIS is not inferior to ACLR with hamstring autograft in terms of rates of clinical outcomes, knee stability, risk of failure, complications, and revision surgery. Therefore, ACLr with DIS may be a viable alternative to ACLR with hamstring autograft in selected patients. LEVEL OF EVIDENCE: Level I, systematic review of Level I studies.

Interventional treatments for low back pain due to sacroiliac joint dysfunction: a systematic review of the literature.

PURPOSE: This systematic review aimed to report the current evidence in the literature about the efficacy of interventional treatments in the management of low back pain (LBP) due to sacroiliac joint dysfunction. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, EMBASE, Scopus, CINAHL, Cochrane Library, and CENTRAL bibliographic databases were searched. The search was performed from October to December 2021, and articles from the inception of the database to December 2021 were searched. RESULTS: Fourteen studies were included for qualitative synthesis. Five studies used the traditional radiofrequency approach (tRF), five studies used cooled radiofrequency approach (cRF), one study used botulinum toxin (BT), two studies used steroid injection, triamcinolone (TA) and local anesthetics injections, and one study used pulsed radiofrequency (PRF) denervation. Two studies used sham as a comparator. CONCLUSIONS: Cooled radiofrequency seems to be the most effective treatment in improving pain and functionality, while intra-articular injections are helpful only as diagnostic tools. However, due to the lack of high-quality studies, it was not possible to draw significant conclusions.

Rehabilitation of sick-listed LBP patients in occupational health with collaboration of the workplace.

The aim was to evaluate if rehabilitation procedures including occupational health (OH) and workplace participation increase return to work (RTW) rates among patients with subacute and chronic low back pain (LBP). A systematic review of randomized controlled trials was conducted using the PubMed and Cochrane databases. Main outcomes were RTW and days of sick leave. Interventions needed to be multidisciplinary including both OH and active workplace involvement in rehabilitation. Out of 1073 potentially eligible references, 8 met the inclusion criteria. Three studies had OH and 5 case managers involved in rehabilitation. Rehabilitation involving both OH and workplace improved RTW and decreased the number of sick leave days among LBP patients. Having case managers involved had no effect in RTW. In order to improve RTW, workplace visits and work ability meetings (WAMs) between OH and workplace are essential components in the rehabilitation process among patients with chronic LBP. Based on the study results, the authors suggest utilizing these co-operative interventions with workplaces in OH. High quality research investigating only the effect of WAMs in OH setting is needed in future. Int J Occup Med Environ Health. 2024;37(1):3-17.

Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro 3D alginate-bead culture model.

Background: Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ-MSC)-derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate-bead culture model. Methods: After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100 µg/mL WJ-MSC-EVs. Cell proliferation and viability were assessed by flow cytometry and live/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9-dimethylmethylene blue assays. hNPCs in alginate beads were paraffin-embedded and stained for histological analysis (hematoxylin-eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (MMP1, MMP13, ADAMTS5, IL6, NOS2), anabolic (ACAN), and hNPC marker (SOX9, KRT19) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis. Results: Treatment with WJ-MSC-EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment. Conclusions: WJ-MSC-derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.

Threats and opportunities of using ChatGPT in scientific writing-The risk of getting spineless.

ChatGPT and AI chatbots are revolutionizing several science fields, including medical writing. However, the inadequate use of such advantageous tools can raise numerous methodological and ethical issues.

The burden of low back pain in children and adolescents with overweight and obesity: from pathophysiology to prevention and treatment strategies.

Nonspecific low back pain (LBP) is one of the most common causes of disability, affecting all individuals at least once in their lifetime. Such a condition is also becoming increasingly frequent in the pediatric population, especially in children and adolescents with overweight/obesity. Furthermore, new-onset LBP during adolescence has been demonstrated to be a strong predictor of developing LBP later in life, contributing to poorer outcomes and increasing social and medical costs. Several causes and different mechanisms have been considered for the development of LBP in pediatric individuals affected by obesity. For this reason, planning adequate prevention and treatment strategies, mainly through conservative lifestyle changes, would be crucial to anticipate the negative consequences of persisting LBP in adulthood. The aim of this narrative review was to characterize the relationship between LBP and overweight/obesity in the pediatric population, highlighting epidemiological and pathophysiological aspects. In addition, prevention and treatment approaches will be reviewed considering the need to reduce the burden of LBP on this population. According to our search, LBP was more frequent in children and adolescents with overweight and obesity and has been associated with several anthropometric and lifestyle factors, including lumbar hyperlordosis, sedentary habits, physical inactivity, carrying a heavy schoolbag, low vitamin D levels, psychosocial ill-being, and premature intervertebral disc degeneration. Most of these conditions may be addressed with conservative strategies mainly consisting of dietary adjustments, physical exercise, education programs, and physical therapy.

Preoperative Embolization of Vertebral Metastasis: Comprehensive Review of the Literature.

The aim of this review is to determine the safety and efficacy of pre-operative spinal metastases embolization procedures. Two reviewers independently conducted the literature search (on MEDLINE databases), including in the review of all the studies that used pre-operative TAE to treat spinal metastases. Twelve articles on pre-operative spinal metastases embolization were selected. Most of the studies demonstrated the low complication rate of pre-operative embolization. The most important study strength is that there are very few reviews in the literature with the setting on pre-operative vertebral metastases embolization. A limitation of the review is that the studies included were predominately retrospective case-control studies, increasing the risk of bias in the primary data. Plus, divergent surgical and embolization procedures were performed in the studies, causing a potential risk of bias in the pooled results. We can conclude that preoperative arterial embolization of vertebral metastases is a safe, well-tolerated technique that reduces surgical blood loss and facilitates surgical tumor resection.

The Effect of Transitioning to Remote Working in Patients Affected by Chronic Low Back Pain: A Cross-Sectional Study.

OBJECTIVE: To assess the effect of transitioning to remote working during the coronavirus disease 2019 pandemic in a population of adults affected by chronic low back pain (cLBP). METHODS: An online questionnaire was sent by email to teleworkers affected by cLBP. Demographic data, remote working features and tasks, and LBP burden were analyzed. The psychological burden of remote working was evaluated with the World Health Organization Five Well-Being Index and the Patient Health Questionnaire-2. LBP severity was evaluated using a visual analogue scale. LBP-related disability was assessed using the Oswestry Disability Index. The effect of LBP on working capacity was examined with the Occupational Role Questionnaire. Independent risk factors related to LBP worsening were identified using a multivariate logistic regression model. RESULTS: During remote working, LBP severity was significantly higher compared to previous in-person working (p < 0.0001), as well as average weekly work hours (p < 0.001). Furthermore, the risk of LBP worsening was associated with higher depression scores (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.00-1.91; p = 0.048), increased stress levels (OR: 3.00, 95% CI: 1.04-8.65; p = 0.042), and being divorced (OR: 4.28, 95% CI: 1.27-14.47; p = 0.019). Conversely, living with others (OR: 0.24, 95% CI: 0.07-0.81; p = 0.021), and reporting unchanged stress levels (OR: 0.22, 95% CI: 0.08-0.65; p = 0.006) were associated with a lower risk of LBP worsening. CONCLUSION: Our findings highlight key factors to consider for improving remote workers' physical and mental wellbeing and decrease their LBP burden.

Oil-Water Emulsion Flocculation through Chitosan Desolubilization Driven by pH Variation.

Water pollution is a major concern in our modern age. The contamination of water, as a valuable and often limited resource, affects both the environment and human health. Industrial processes such as food, cosmetics, and pharmaceutical production also contribute to this problem. Vegetable oil production, for example, generates a stable oil/water emulsion containing 0.5-5% oil, which presents a difficult waste disposal issue. Conventional treatment methods based on aluminum salts generate hazardous waste, highlighting the need for green and biodegradable coagulant agents. In this study, the efficacy of commercial chitosan, a natural polysaccharide derived from chitin deacetylation, has been evaluated as a coagulation agent for vegetable oil emulsions. The effect of commercial chitosan was assessed in relation to different surfactants (anionic, cationic, and nonpolar) and pH levels. The results demonstrate that chitosan is effective at concentrations as low as 300 ppm and can be reused, providing a cost-effective and sustainable solution for oil removal. The flocculation mechanism relies on the desolubilization of the polymer, which acts as a net to entrap the emulsion, rather than solely relying on electrostatic interactions with the particles. This study highlights the potential of chitosan as a natural and ecofriendly alternative to conventional coagulants for the remediation of oil-contaminated water.

Innovative quantitative magnetic resonance tools to detect early intervertebral disc degeneration changes: a systematic review.

BACKGROUND CONTEXT: Low back pain (LBP) is the leading cause of disability worldwide, with a tremendous socioeconomic burden. It is mainly caused by intervertebral disc degeneration (IDD), a progressive and age-related process. Due to its ability to accurately characterize intervertebral disc morphology, magnetic resonance imaging (MRI) has been established as one of the most valuable tools in diagnosing IDD. Innovative quantitative MRI (qMRI) techniques able to detect the earliest signs of IDD have been increasingly reported. PURPOSE: To systematically review available reports on the application of novel qMRI techniques to detect early IDD changes. STUDY DESIGN: Systematic literature review. METHODS: A systematic search of PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL and Cochrane databases was performed through January 21, 2023. Randomized and nonrandomized studies on innovative qMRI tools able to diagnose early biochemical and architectural IDD changes in patients with or without discogenic LBP were searched. Data on study population, follow-up time (when applicable) and MRI sequence used were recorded. The QUADAS-2 tool was utilized to assess the risk of bias of included studies. RESULTS: A total of 39 articles published between 2005 and 2022 resulted from the search. All novel qMRI techniques showed an increased capacity to detect early IDD changes thanks to the ability to assess subtle alterations of water content, proteoglycan and glycosaminoglycan concentration, and increased levels of catabolic biomarkers compared to conventional MRI. CONCLUSIONS: Innovative qMRI techniques have proven effective in identifying premature IDD changes. Further studies are needed to validate their application in wider populations and confirm their applicability in the clinical setting.

Irisin inhibits tenocyte response to inflammation in vitro: New insights into tendon-muscle cross-talk.

Tendinopathy is one of the most common musculoskeletal disorders with significant repercussions on quality of life and sport activities. Physical exercise (PE) is considered the first-line approach to treat tendinopathy due renowned mechanobiological effects on tenocytes. Irisin, a recently identified myokine released during PE, has been recognized for several beneficial effects towards muscle, cartilage, bone, and intervertebral disc tissues. The aim of this study was to evaluate the effects of irisin on human primary tenocytes (hTCs) in vitro. Human tendons were harvested from specimens of patients undergoing anterior cruciate ligament reconstruction (n = 4). After isolation and expansion, hTCs were treated with RPMI medium (negative control), interleukin (IL)-1ß or tumor necrosis factor-α (TNF-α) (positive controls; 10 ng/mL), irisin (5, 10, 25 ng/mL), IL-1ß or TNF-α pretreatment and subsequent co-treatment with irisin, pretreatment with irisin and subsequent co-treatment with IL-1ß or TNF-α. hTC metabolic activity, proliferation, and nitrite production were evaluated. Detection of unphosphorylated and phosphorylated p38 and ERK was performed. Tissue samples were analyzed by histology and immunohistochemistry to evaluate irisin αVß5 receptor expression. Irisin significantly increased hTC proliferation and metabolic activity, while reducing the production of nitrites both before and after the addition of IL-1ß and TNF-α. Interestingly, irisin reduced p-p38 and pERK levels in inflamed hTCs. The αVß5 receptor was uniformly expressed on hTC plasma membranes, supporting the potential binding of irisin. This is the first study reporting the capacity of irisin to target hTCs and modulating their response to inflammatory stresses, possibly orchestrating a biological crosstalk between the muscle and tendon.

Mesenchymal stem cell-derived secretome enhances nucleus pulposus cell metabolism and modulates extracellular matrix gene expression in vitro.

Introduction: Intradiscal mesenchymal stromal cell (MSC) therapies for intervertebral disc degeneration (IDD) have been gaining increasing interest due to their capacity to ameliorate intervertebral disc metabolism and relieve low back pain (LBP). Recently, novel investigations have demonstrated that most of MSC anabolic effects are exerted by secreted growth factors, cytokines, and extracellular vesicles, collectively defined as their secretome. In this study, we aimed to evaluate the effect of bone-marrow-MSCs (BM-MSCs) and adipose-derived stromal cells (ADSCs) secretomes on human nucleus pulposus cells (hNPCs) in vitro. Methods: BM-MSCs and ADSCs were characterized according to surface marker expression by flow cytometry and multilineage differentiation by Alizarin red, Red Oil O and Alcian blue staining. After isolation, hNPCs were treated with either BM-MSC secretome, ADSC secretome, interleukin (IL)-1ß followed by BM-MSC secretome or IL-1ß followed by ADSC secretome. Cell metabolic activity (MTT assay), cell viability (LIVE/DEAD assay), cell content, glycosaminoglycan production (1,9-dimethylmethylene blue assay), extracellular matrix and catabolic marker gene expression (qPCR) were assessed. Results: 20% BM-MSC and ADSC secretomes (diluted to normal media) showed to exert the highest effect towards cell metabolism and were then used in further experiments. Both BM-MSC and ADSC secretomes improved hNPC viability, increased cell content and enhanced glycosaminoglycan production in basal conditions as well as after IL-1ß pretreatment. BM-MSC secretome significantly increased ACAN and SOX9 gene expression, while reducing the levels of IL6, MMP13 and ADAMTS5 both in basal conditions and after in vitro inflammation with IL-1ß. Interestingly, under IL-1ß stimulation, ADSC secretome showed a catabolic effect with decreased extracellular matrix markers and increased levels of pro-inflammatory mediators. Discussion: Collectively, our results provide new insights on the biological effect of MSC-derived secretomes on hNPCs, with intriguing implications on the development of cell-free approaches to treat IDD.