IL24 Expression in Synovial Myofibroblasts: Implications for Female Osteoarthritis Pain through Propensity Score Matching Analysis.

(1) Introduction: Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) Methods: To assess gender-specific variations, we analyzed myofibroblast marker expression and IL24 levels in synovial tissue samples from propensity-matched male and female OA patients (each n = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between IL24 expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between IL24 and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients (n = 5), and IL24 expression was compared between these subsets. (3) Results: Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and IL24 compared to males. IL24 expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed IL24 compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) Conclusions: Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA's multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium.

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1-CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.

Biofabrication of engineered blood vessels for biomedical applications.

To successfully engineer large-sized tissues, establishing vascular structures is essential for providing oxygen, nutrients, growth factors and cells to prevent necrosis at the core of the tissue. The diameter scale of the biofabricated vasculatures should range from 100 to 1,000 µm to support the mm-size tissue while being controllably aligned and spaced within the diffusion limit of oxygen. In this review, insights regarding biofabrication considerations and techniques for engineered blood vessels will be presented. Initially, polymers of natural and synthetic origins can be selected, modified, and combined with each other to support maturation of vascular tissue while also being biocompatible. After they are shaped into scaffold structures by different fabrication techniques, surface properties such as physical topography, stiffness, and surface chemistry play a major role in the endothelialization process after transplantation. Furthermore, biological cues such as growth factors (GFs) and endothelial cells (ECs) can be incorporated into the fabricated structures. As variously reported, fabrication techniques, especially 3D printing by extrusion and 3D printing by photopolymerization, allow the construction of vessels at a high resolution with diameters in the desired range. Strategies to fabricate of stable tubular structures with defined channels will also be discussed. This paper provides an overview of the many advances in blood vessel engineering and combinations of different fabrication techniques up to the present time.

This review covers several aspects and advancements of engineered blood vessel biofabrication, which are essential for establishment of large-sized tissues in different areas of biomedical applications.

Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis.

Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells' (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions.

CD39+CD55- Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee.

Recent studies utilizing single-cell analysis have unveiled the presence of various fibroblast (Fb) subsets within the synovium under inflammatory conditions in osteoarthritis (OA), distinguishing them from those in rheumatoid arthritis (RA). Moreover, it has been reported that pain in knee OA patients is linked to specific fibroblast subsets. Single-cell expression profiling methods offer an incredibly detailed view of the molecular states of individual cells. However, one limitation of these methods is that they require the destruction of cells during the analysis process, rendering it impossible to directly assess cell function. In our study, we employ flow cytometric analysis, utilizing cell surface markers CD39 and CD55, in an attempt to isolate fibroblast subsets and investigate their relationship with OA pathology. Synovial tissues were obtained from 25 knee OA (KOA) patients. Of these, six samples were analyzed by RNA-seq (n = 3) and LC/MS analysis (n = 3). All 25 samples were analyzed to estimate the proportion of Fb (CD45-CD31-CD90+) subset by flow cytometry. The proportion of Fb subsets (CD39+CD55- and CD39-CD55+) and their association with osteoarthritis pathology were evaluated. CD39+CD55- Fb highly expressed myogenic markers such as CNN1, IGFBP7, MYH11, and TPM1 compared to CD39-CD55+ Fb. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of upregulated differentially expressed genes (DEGs) in CD39+CD55- Fb identified the Apelin pathway and cGMP-PKC-signaling pathway as possibly contributing to pain. LC/MS analysis indicated that proteins encoded by myogenic marker genes, including CNN1, IGFBP7, and MYH11, were also significantly higher than in CD39-CD55+ Fb. CD39-CD55+ Fb highly expressed PRG4 genes and proteins. Upregulated DEGs were enriched for pathways associated with proinflammatory states ('RA', 'TNF signaling pathway', 'IL-17 signaling pathway'). The proportion of CD39+CD55- Fb in synovium significantly correlated with both resting and active pain levels in knee OA (KOA) patients (resting pain, ρ = 0.513, p = 0.009; active pain, ρ = 0.483, p = 0.015). There was no correlation between joint space width (JSW) and the proportion of CD39+CD55- Fb. In contrast, there was no correlation between the proportion of CD39-CD55+ Fb and resting pain, active pain, or JSW. In conclusion, CD39+CD55- cells exhibit a myofibroblast phenotype, and its proportion is associated with KOA pain. Our study sheds light on the potential significance of CD39+CD55- synovial fibroblasts in osteoarthritis, their myofibroblast-like phenotype, and their association with joint pain. These findings provide a foundation for further research into the mechanisms underlying fibrosis, the impact of altered gene expression on osteoarthritic joints, and potential therapeutic strategies.

Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts.

Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.

Expression of Apelin in Rotator Cuff Tears and Examination of Its Regulatory Mechanism: A Translational Study.

OBJECTIVES: Inflammatory mediators play important roles in the pain associated with rotator cuff tears (RCTs), but their underlying mechanisms are unclear. Apelin, a neuropeptide, is upregulated under inflammatory conditions and possibly contributes to pain induced by rotator cuff tears. This translational study aimed to examine apelin expression and regulation by tumor necrosis factor alpha (TNF-α) in patients with RCT and in rat RCT models. METHODS: Synovial tissues were harvested from the glenohumeral joints of the shoulders in 46 patients who underwent arthroscopic Bankart repair for recurrent shoulder dislocations (RSDs) or arthroscopic rotator cuff repair for RCTs. The harvested tissues were extracted and processed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rats underwent sham or RCT surgery; the rotator cuff tissues were extracted 1, 7, 14, 28, and 56 days after surgery and analyzed for mRNA expression levels of the TNF-α and apelin using RT-PCR. The cultured rotator cuff cells (RCCs) were stimulated with TNF-α to examine their role in the regulation of apelin expression. RESULTS: Apelin expression was higher in the RCT group than in the RSD group and significantly correlated with pain intensity. In rats, the expression was also higher in RCT. Apelin expression significantly increased during the acute and chronic phases in rats. CONCLUSIONS: In cultured RCCs, apelin mRNA levels significantly increased after TNF-α stimulation. Apelin levels were regulated by TNF-α and were highly expressed in patients with RCT and rats in RCT models. Thus, apelin may be a new pain management target for RCTs.

Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight.

While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes ß-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m2) and overweight (25-29.99 kg/m2). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required.

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

In situ-formed hyaluronan gel/BMP-2/hydroxyapatite composite promotes bone union in refractory fracture model mice.

BACKGROUND: A combination of synthetic porous materials and BMP-2 has been used to promote fracture healing. For bone healing to be successful, it is important to use growth factor delivery systems that enable continuous release of BMP-2 at the fracture site. We previously reported that in situ-formed gels (IFGs) consisting of hyaluronan (HyA)-tyramine (TA), horseradish peroxidase and hydrogen peroxide enhance the bone formation ability of hydroxyapatite (Hap)/BMP-2 composites in a posterior lumbar fusion model. OBJECTIVE: We examined the effectiveness of IFGs-HyA/Hap/BMP-2 composites for facilitating osteogenesis in refractory fracture model mice. METHODS: After establishing the refractory fracture model, animals were either treated at the site of fracture with Hap harboring BMP-2 (Hap/BMP-2) or IFGs-HyA with Hap harboring BMP-2 (IFGs-HyA/Hap/BMP-2) (n = 10 each). Animals that underwent the fracture surgery but did not receive any treatment were considered the control group (n = 10). We determined the extent of bone formation at the fracture site according to findings on micro-computed tomography and histological studies four weeks following treatment. RESULTS: Animals treated with IFGs-HyA/Hap/BMP-2 demonstrated significantly greater bone volume, bone mineral content and bone union than those treated with vehicle or IFG-HyA/Hap alone. CONCLUSIONS: IFGs-HyA/Hap/BMP-2 could be an effective treatment option for refractory fractures.

Posterior Spinal Fusion Surgery for Neuromuscular Disease Patients with Severe Scoliosis Whose Cobb Angle Was over 100 Degrees.

Background and objectives: Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre- or intraoperative traction would be effective for severe spinal deformities but would be invasive. This study aimed to evaluate the outcomes of PSF-only surgery for patients with severe NMS with a Cobb angle > 100°. Materials and Methods: Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF-only surgery for scoliosis with a Cobb angle > 100° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings, including Cobb angle and pelvic obliquity (PO) in the sitting position pre- and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. Results: The mean duration of surgery was 338 min, intraoperative blood loss was 1440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group were significantly higher than those in the L5 group. Conclusions: Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF surgery without anterior release or any intra-/preoperative traction showed satisfactory outcomes, including acceptable scoliosis correction and improved clinical findings, even in patients with extremely severe NMS. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

Intraoperative Blood Loss at Different Surgical-Procedure Stages during Posterior Spinal Fusion for Idiopathic Scoliosis.

Background and Objectives: Several predictive factors have been reportedly associated with intraoperative total blood loss (TBL) during posterior spinal fusion (PSF) for idiopathic scoliosis (IS). To reduce TBL, preoperative factors and interoperative factors are considered important. However, there are few reports that have evaluated bleeding patterns according to surgical stages. This study aimed to elucidate bleeding patterns at different surgical stages and determine the predictive factors for TBL during PSF surgery in patients with IS. Materials and Methods: Preoperative data, radiographic parameters, and intraoperative data of patients undergoing PSF for IS were retrospectively collected. We divided the patients into six stages: stage 1, exposure; stage 2, implant placement; stage 3, release; stage 4, correction; stage 5, bone grafting; and stage 6, closure; then we reviewed the blood loss and bleeding speed. Multiple-regression analysis was performed to generate a predictive formula for blood loss using preoperative and intraoperative factors, including blood loss at stage 1, as explanatory variables. Results: Forty-five patients (mean age: 17.6 years) were included. The mean operative time and TBL were 287.9 min and 756.5 mL, respectively. Blood loss was the highest at stage 3, followed by stage 4. Bleeding speed was the highest at stage 4, followed by stage 3. Bleeding speeds at stages 3 and 4 were significantly higher than those at stages 1 and 2. Preoperative Cobb angle, activated partial thromboplastin time (aPTT), number of fused vertebrae, and blood loss at stage 1 were significant contributing factors. Conclusions: Blood loss and bleeding speed during the release and correction stages were high. Specifically, bleeding speed significantly increased during and after the release procedure. The preoperative Cobb angle, aPTT, number of fixed vertebrae, and blood-loss volume during PSF were significantly associated with TBL. Our findings would be helpful for reducing TBL in patients undergoing PSF for IS.

Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain.

Pain, the primary symptom of osteoarthritis (OA), reduces both the quality and quantity of life for patients. The pathophysiology of OA pain is complex and often difficult to explain solely by radiological structural changes. One reason for this discrepancy is pain sensitization (peripheral sensitization [PS] and central sensitization [CS]) in OA. Thus, an understanding of pain sensitization is important when considering treatment strategies and development for OA pain. In recent years, pro-inflammatory cytokines, nerve growth factors (NGFs), and serotonin have been identified as causative agents that induce peripheral and central sensitization and are becoming therapeutic targets for OA pain. However, the characteristics of the clinical manifestations of pain sensitization elicited by these molecules remain unclear, and it is not well understood who among OA patients should receive the therapeutic intervention. Thus, this review summarizes evidence on the pathophysiology of peripheral and central sensitization in OA pain and the clinical features and treatment options for this condition. While the majority of the literature supports the existence of pain sensitization in chronic OA pain, clinical identification and treatment of pain sensitization in OA are still in their infancy, and future studies with good methodological quality are needed.

A Modified Sliding-Lengthening Approach to Tendon Lengthening with a Locking Mechanism Suture: A Technical Note.

There are various techniques used for tendon lengthening, of which Z-lengthening and sliding-lengthening are the most frequently performed. In patients with cerebral palsy, tendon lengthening may often be necessary at multiple sites. However, they can cause various complications, such as inaccurate extension, overextension, and a lack of tendon continuity. We modified the sliding-lengthening technique with a locking mechanism to address these issues. This technical note aims to describe the surgical technique and pitfalls associated with the modified sliding-lengthening approach and suture locking mechanism. The tendon was exposed and stabilized using sterilized spitz tubes and was then threaded so that each loop length was equivalent to the amount of tendon extension. Symmetrical hemisection of both ends of the tendon was performed, and the tendon was carefully extended to create a tense loop. The modified sliding-lengthening technique with the locking suture mechanism may be an advantageous method that accurately addresses extension volume, prevents hyperextension, and maintains tendon continuity, even when smaller incisions are used.

Effect of spheroid size on gene expression profiles of a mouse mesenchymal stem cell line in spheroid culture.

BACKGROUND: Mesenchymal stem cell (MSC)-based therapies offer potential for bone repair. MSC spheroid cultures may harbor enhanced therapeutic potential over MSC monolayers through increased secretion of trophic factors. However, the impact of spheroid size on trophic factor expression is unclear. OBJECTIVE: We investigated the effect of spheroid size on trophic factor-related gene expression. METHODS: KUM10, a murine MSC line was used. RNA-seq was used to screen the transcriptional profiles of MSC monolayer and spheroid cultures. Differentially expressed genes identified in RNA-seq were evaluated by q-PCR in cultures of 5 × 104 (S group), 5 × 105 (M group), 5 × 106 (L group) cells/well. RESULTS: Comparison of expression levels between KUM10 monolayer and spheroid cultures identified 2140 differentially expressed genes, of which 1047 were upregulated and 1093 were downregulated in KUM10 spheroids. Among these, 12 upregulated genes (Bmp2, Fgf9, Fgf18, Ngf, Pdgfa, Pdgfb, Tgfb1, Vegfa, Vegfc, Wnt4, Wnt5a, Wnt10a) were associated with secretory growth factors. Of these, expression of Fgf9, Fgf18, Vegfa and Vegfc was elevated in the L group, and Pdgfb and Tgfb1 was elevated in the S group. CONCLUSIONS: Spheroid size may impact trophic factor expression. Our results will be useful for future studies assessing the utility of MSC spheroids for treating bone injury.

Mild inflammation persists in the glenohumeral joint of patients with shoulder instability: Cross-sectional study.

Objective: Approximately two-thirds of patients with history of shoulder dislocation may develop osteoarthritis (OA) of the glenohumeral joint. However, the biochemical mechanisms underlying the association between dislocation and OA are largely unknown. This study aimed to investigate macrophage markers and inflammatory cytokine expression associated with shoulder instability (SI) in comparison to rotator cuff tears (RCTs). Design: This study included 30 patients with SI and 30 patients with RCTs. Synovial membrane samples were harvested from the rotator interval during the arthroscopic anatomical repair for both groups. The localization of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and cluster of differentiation (CD) 68 in synovial membranes was determined by immunohistochemistry. Transcript-level expressions of the inflammatory cytokines (TNFA and IL1B) and macrophage markers pan-CD68 and -M1 (CD80 and CD86) were quantified. CD80 and CD86 expression in macrophages from the SI group was confirmed using flow cytometry. Results: TNF-α, IL-1ß, and CD68 were expressed in the synovial lining layer of the synovial tissue in both groups. In addition, the mRNA expressions of TNFA, IL1B, CD68, and CD80 were significantly higher in the SI group compared to the RCT group (P â€‹= â€‹0.012, 0.014, 0.022, 0.003, respectively). In samples from the SI group, 96.3% of CD68+/CD14+ macrophages were CD86-positive, whereas 2.5% of CD68+/CD14+/CD86+ cells were CD80-positive. Conclusions: Patients with SI had higher mRNA levels of TNFA, IL1B, CD68, and CD80 than those with RCTs. These findings may partially explain the biochemical mechanism underlying the frequent development and progression of osteoarthritis in patients with SI.

ß2-Microglobulin Elevates COL5A1 mRNA in the Subsynovial Connective Tissue of Patients Receiving Hemodialysis With Carpal Tunnel Syndrome.

Background Although carpal tunnel syndrome (CTS) is frequently observed in patients undergoing long-term hemodialysis (HD), exactly how CTS arises is unknown. Here, we examined levels of COL5A1 in the subsynovial connective tissue (SSCT) of patients receiving HD and studied its potential regulation by ß2-microglobulin (Β2-MG) in SSCT-derived cells (SSCTCs). Methods We extracted SSCT samples from 67 patients with CTS (49 non-HD and 18 HD) during carpal tunnel release. The samples were subjected to quantitative polymerase chain reaction (qPCR) to determine COL5A1 expression. Further, to examine the potential regulation of COL5A1 expression by Β2-MG, SSCTCs were stimulated in the absence (control) or presence of 10 µg/ml Β2-MG. Results The HD group showed significantly elevated COL5A1 levels compared to the non-HD group (P=0.027). Moreover, treating SSCTCs with Β2-MG for 24 h increased the mRNA expression of COL5A1 relative to control conditions (P=0.013). Conclusions Elevated COL5A1 expression may form part of the mechanism underlying the development of CTS, and Β2-MG may play a role in promoting COL5A1 expression in HD patients.

Increased Synovial CD14 mRNA Expression and Proportion of CD14high Subsets in Early-Stage Hip Osteoarthritis: Propensity Matched Score Analysis.

The pathophysiology of early-stage hip osteoarthritis (EOA) is not fully understood. Although a previous study in an age-unmatched cohort reported that the number of macrophages was increased in knee EOA compared to late OA (LOA), it remained unclear whether increased macrophages in EOA accurately reflect EOA pathology. We investigated the differences in CD14 expression levels between EOA and LOA using age-unmatched and -matched cohorts. Synovial tissues were obtained from 34 EOA (Tönnis grades 0 and 1) and 80 LOA (Tönnis grades 2 and 3) patients. To correct for differences in demographics between patients with LOA and EOA, we also created propensity score-matched cohorts (16 EOA and 16 LOA). CD14 expression and its association with pain was estimated in LOA and EOA before and after propensity matching. We performed flow cytometry on tissues from the 16 patients, with 8 from each group, to assess for CD14+ subsets in the cells. The CD14 expression in EOA was higher than that in LOA both before and after propensity matching. The proportion of CD14high subsets in EOA was higher than that in LOA. The CD14 expression was associated with pain in EOA before matching. However, no difference was observed between the pain and CD14 expression after matching in EOA. The increased CD14 expression and the proportion of CD14high subsets may be important features associated with hip EOA pathology. To accurately compare early and late OA, the analysis of a propensity score-matched cohort is necessary.

Increased NMUR1 Expression in Mast Cells in the Synovial Membrane of Obese Osteoarthritis Patients.

Obesity is a risk factor for knee osteoarthritis (KOA). Neuromedin U (NMU) and NMU receptors (NMUR1 and NMUR2) are associated with obesity-related disorders and found in mast cells (MCs), which are elevated in osteoarthritis. However, NMU/NMUR expression was not examined in the synovial membrane (SM) or synovial MCs of obese osteoarthritis patients. We compared expression of NMU, NMUR1, NMUR2, and the mast cell (MC) marker, CPA3, in the SM of KOA patients categorized as normal weight (NW; BMI < 25 kg/m2, n = 79), overweight (OW; BMI ≥ 25 and <30 kg/m2, n = 87), and obese (OB; ≥30 kg/m2, n = 40). To study NMU/NMUR expression in MCs, we compared the MC-rich fraction (MC-RF), CD88(+) MC-RF, and CD88(−) MC-RF, extracted using magnetic isolation, with the MC-poor fraction (MC-PF). While NMU and NMUR2 expression were comparable, NMUR1 was significantly elevated in OW and OB compared to NW. Moreover, CPA3 levels were significantly greater in OB than NW. NMUR1 and CPA3 expression were significantly higher in both the CD88(+) and CD88(−) MC-RF than MC-PF. Therefore, NMUR1 expression was elevated in the SM of OB KOA patients, and its expression was found in MCs. Further investigation to analyze the NMU/NMUR1 pathway in MC may provide a link between obesity and KOA pathology.

Is bone marrow oedema in patients with labral tear an indicator of hip pain?

BACKGROUND: Hip labral tear (LT) causes various degrees of hip pain, for which there are few objective measures. Bone marrow oedema (BME), characterized by a diffuse, widely spreading change in the bone marrow, is observed in some patients with LT. However, its pathological role has not been fully understood. The purpose of this study was to investigate the prevalence of BME on hip magnetic resonance imaging (MRI) in patients with LT and to determine whether BME was an objective indicator of hip pain. METHODS: In total, 84 patients with LT who underwent MRI scanning under the same conditions were included. We determined the presence or absence of BME and its size on MRI and evaluated the relationships between BME and sex, age, and pain and total scores on the modified Harris hip score (MHHS). In addition, we collected data on surgical treatments such as hip arthroscopy within a one-year follow-up period and examined whether the presence of BME affected the course of therapy. RESULTS: BME was found in 34.5% of patients. MHHS pain and total scores were significantly lower in patients with BME (MHHS pain score: non-BME vs. BME ≤ 1 cm: p = 0.022, non-BME vs. BME > 1 cm: p < 0.001; MHHS total score: non-BME vs. BME ≤ 1 cm: p = 0.131, non-BME vs. BME > 1 cm: p = 0.027). The presence of BME did not differ between patients who did and did not undergo surgery during follow-up (p = 0.563). CONCLUSION: BME on MRI in patients with LT might be an indicator of hip pain and hip joint dysfunction.