Conservative treatment of congenital radial head subluxation and non-traumatic elbow locking: A case report.

Congenital radial head subluxation is relatively rare and may be overlooked due to mild symptoms. The diagnosis mainly relies on imaging and history. Observation is an option for those with insignificant symptoms, while surgical intervention, such as ulnar osteotomy or arthroscopy, is often required when dysfunction exists. A 30-year-old man was admitted with congenital radial head dislocation, which was treated with manipulative repositioning. During follow-up, the patient regained the original mobility of the elbow joint and had no recurrence of dislocation. In conclusion, in adults with congenital dislocation of the radial head, we recommend conservative treatment as a first step.

Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study.

Purpose: To explore the effect of AFN on knee function and complications in patients after TKA. Methods: We evaluated 150 patients undergoing unilateral TKA, specifically including 102 patients with varying degrees of AFN after selection. They were divided into four groups based on AFN grade. About 48 patients did not produce AFN, 63 patients were grade I, 29 patients were grade II, and 10 patients were grade III. All patients were followed up for 24 months, and knee function, pain, complications, and other indicators were compared between the four groups. Correlation analysis and regression analysis were used to study the relationship between AFN and other indicators. Results: Two cases of periprosthetic fractures (PPF) occurred in our study, with an incidence of 1.35%, which did not show a significant association with AFN. The changes in knee social score (ΔKSS), Western Ontario and McMaster Universities Osteoarthritis Index (ΔWOMAC), and postoperative anterior knee pain visual analog scale (VAS) score were higher in patients with AFN than in those without. Particularly, grades II and III AFN demonstrated superior efficacy. Pearson's correlation analysis showed that AFN grade is positively correlated with both ΔKSS and ΔWOMAC (r = 0.44, P < 0.001), and AFN grade had a negative correlation with the anterior knee pain VAS (r = -0.250, P < 0.05). In linear regression analysis, AFN grade was positively correlated with both ΔKSS (ß = 5.974, 95% CI: 3.968-7.981, P < 0.001) and ΔWOMAC (ß = 6.356, 95% CI: 4.223-8.490, P < 0.001). Besides that, there was a negative correlation between AFN grade and anterior knee pain (ß = 5.974, 95% CI: 3.968-7.981, P < 0.05). Conclusion: Patients with grade II and III AFN who underwent TKA exhibited better knee function and lower levels of anterior knee pain post-surgery.

Global burden and epidemic trends of gout attributable to high body mass index from 1990 to 2019.

Introduction: Gout is an inflammatory and metabolic disease characterized by arthritis and elevation of the serum uric acid (SUA) level. More and more studies have shown that high body mass index (BMI) has become one of the most important risk factors for gout. Material and methods: We used the data of gout burden attributed to high body mass index (BMI) from global burden of disease (GBD) study 2019 to provide insights for reducing the global burden of gout. Results: From 1990 to 2019, the prevalence and DALYs of gout caused by high BMI worldwide has been increasing. The burden of gout caused by high BMI is heavier in the elderly male group and regions with high SDI worldwide. Conclusions: Our findings provide evidence for the burden of gout caused by high BMI. Developing a weight management plan and lifestyle habits for groups severely affected by gout will effectively reduce the global disease and economic burden.

Intra-articular injection of tranexamic acid in patients with haemophilia arthritis: retrospective controlled study in total knee arthroplasty.

PURPOSE: Total knee arthroplasty is the main method for the treatment of advanced haemophilic knee arthritis. Due to the particularity of hemophilia, the blood management plan is the focus of the perioperative period for haemophilia patients. This study aimed to investigate the clinical effect and safety of intra-articular injection of tranexamic acid in patients with haemophilia. METHODS: This is a retrospective study. According to whether tranexamic acid is used or not, patients are divided into tranexamic acid group (n=30) and non-tranexamic acid group (n=29). Total blood loss, intraoperative blood loss, complete blood count, total amount of coagulation factor VIII (FVIII) usage, coagulation biomarkers, inflammatory biomarkers, knee range of motion, knee joint function, pain status, complication rate, and patient satisfaction were assessed and compared at a mean follow-up of 16 months. RESULTS: Injecting tranexamic acid into the knee joint cavity can effectively reduce the hidden blood loss and total blood loss (P<0.001), and reduce the patient's early postoperative inflammation biomarkers, pain status, and limb swelling. Therefore, the patient can obtain a better range of motion following total knee arthroplasty. In the long run, in terms of joint function and surgical satisfaction, there are no statistically significant differences. In addition, there are no statistically significant differences between the two groups of patients in terms of the total amount of FVIII usage, length of stay, and hospitalization expenses. CONCLUSION: In patients with haemophilia, intra-articular injection of tranexamic acid during total knee arthroplasty can effectively reduce postoperative blood loss, early postoperative inflammation levels, pain and limb swelling, and enable patients to receive higher-quality rehabilitation exercises to get better joint function. Previous studies on TKA in haemophilic patients have already demonstrated the efficacy of intra-articular injections of TXA in reducing postoperative blood loss. Our study confirms this efficacy.

The global magnitude and temporal trend of rheumatoid arthritis burden attributable to smoking from 1990 to 2019.

OBJECTIVES: The relationship between smoking and RA has been confirmed. Most nations have ratified the Framework Convention on Tobacco Control. However, there are considerable regional differences in how effectively tobacco control measures were implemented. This study was carried out to estimate the spatiotemporal trends of smoking-related RA burdens. METHODS: Data were available from the Global Burden of Disease Study 2019 and were analysed by age, sex, year and region. Joinpoint regression analysis was applied to the analysis of temporal trends in the RA burden resulting from smoking over 30 years. RESULTS: From 1990 to 2019, the number of global RA cases increased each year. The age-standardized prevalence, death and disability-adjusted life-year (DALY) rates also increased. However, there was a wave in the changing trend of the age-standardized death rate, with the lowest point in 2012 and the highest point in 1990. Smoking, in particular, was responsible for 11.9% of total RA deaths and 12.8% of total DALYs in 1990 but only 8.5% of total RA deaths and 9.6% of total DALYs in 2019. A greater burden from smoking exposure was borne by men, older adults and people living in high-middle and high sociodemographic index (SDI) countries and regions. Moreover, the UK demonstrated the highest reduction in age-standardized death and DALY rates over the three decades. CONCLUSION: There were reductions in the age-standardized burdens of RA caused by smoking worldwide. Nevertheless, this continues to be an issue in some areas, and efforts to reduce smoking should be made to lessen this growing burden.

Total hip and knee arthroplasty in HIV- and HCV-positive hemophilia patients: short term follow-up of 14 patients.

BACKGROUND: Haemophilic arthropathy (HA) is a common comorbidity of haemophilia. Some people with haemophilia (PWH) were human immunodeficiency virus (HIV)-positive. Arthroplasty is an effective treatment for end-stage HA. This study was carried out to report the effectiveness and satisfaction following total hip arthroplasty (THA) or total knee arthroplasty (TKA) in PWH with HIV. PATIENTS AND METHODS: All patients with haemophilia and HIV undergoing THA or TKA in our centre from January 2015 to June 2020 were reviewed. All patients were followed for at least twenty-four months. The improvements in postoperative indicators were evaluated at the latest follow-up, including the Visual Analogue Scale (VAS) score, range of motion (ROM), and validated joint scores such as Knee Society Score (KSS; clinical and functional) and Harris Hip Score (HHS). The complications and satisfaction were analysed likewise. Those were utilized to weigh the risks and benefits of the procedure in the population. RESULTS: Fourteen patients (7 hips and 14 knees) were included in the study. The follow-up of the THA cohort was 53.3 months (range, 27-82) and the TKA cohort was 50.1 months (range, 25-85), respectively. The average VAS score was ameliorated from 7.3 to 3.0 and 6.6 to 2.8 in the two groups (P < .001, respectively). Similarly, two cohorts (THA and TKA) showed statistically significant changes in the extension and flexion ROM between the preoperative and the latest follow-up (P < .05, P < .001, respectively). Besides, statistically significant differences between the preoperative and final follow-up values of HHS (from 41.6 to 82.3), clinical KSS (from 34.8 to 72.8), and functional KSS (from 42.9 to 73.2) were observed (P < .001, respectively). Notably, there were 4 complications noted among 21 arthroplasties performed, giving a 19.0% complication rate. Based on the satisfaction score, the majority of patients were optimistic about the arthroplasty. CONCLUSION: Given these findings, THA or TKA of the PWH with HIV is a worthwhile procedure and can be performed by an experienced and collaborative multidisciplinary team in a tertiary centre with a good haemophilia care system.

Disruption of Col9a2 expression leads to defects in osteochondral homeostasis and osteoarthritis-like phenotype in mice.

Background/Objective: As one of the branched chains of Type IX collagen (Col9), Collagen IX alpha2 (Col9a2) has been reported to be associated with several orthopedic conditions. However, the relationship between Col9a2 and knee osteoarthritis (KOA) remains to be elucidated. Methods: To probe the relationship between Col9a2 and KOA, we performed a systematic analysis of Col9a2-deficient (Col9a2-/-) mice using whole-mount skeletal staining, Micro-CT (µCT), biomechanics, histomorphometry, immunohistochemistry (IHC), immunofluorescence (IF) and Elisa. Results: We found that the subchondral bone (SCB) in the knee joint of Col9a2-/- mice became sparse and deformed in the early stage, with altered bone morphometric parameters, reduced load-bearing capacity, dysfunctional bone homeostasis (decreased osteogenesis capacity and elevated bone resorption capacity), diminished cartilage proteoglycans and disrupted cartilage extracellular matrix (ECM) anabolism and catabolism compared with the Col9a2+/+ mice. In the late stage, the cartilage degeneration in Col9a2-/- mice were particularly pronounced compared to Col9a2+/+ mice, as evidenced by severe cartilage destruction and a marked reduction in cartilage thickness and area. Conclusion: Overall, Col9a2 is essential for maintaining osteochondral homeostasis in the knee joint of mice, and the absence of this gene is accompanied by distinct sclerosis of the SCB and a reduction in load-bearing capacity; in the late stage, in the lack of SCB stress inhibition, excessive load is consistently exerted on the cartilage, ultimately leading to osteoarthritic-like articular cartilage damage.

Relationship between 25-hydroxy vitamin D and knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

Objective: In order to examine the relationship between 25-hydroxyl vitamin D and knee osteoarthritis (KOA), a meta-analysis of 8 randomized controlled trials (RCTs) publications was hereby performed. Methods: For the purpose of finding pertinent research, the databases of PubMed, Embase and the Cochrane Library were searched. Factors including tibial cartilage volume, joint space width (JSW), synovial fluid volume, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were correspondingly evaluated, and the results were expressed using SMD and 95% confidence intervals (CI). Results: The present meta-analysis evaluated the effects of vitamin D supplementation in patients with knee osteoarthritis, with 3,077 patients included. The results showed that vitamin D administration had a statistically significant impact on the amount of synovial fluid, Visual Analog Scale (VAS) and tibial cartilage. The pain and function scales of the WOMAC scale presented a statistically significant difference, and there was no discernible difference between the vitamin D and placebo groups in the stiffness scale. Additionally, bone marrow lesions and alterations in the diameter of the joint space were not influenced by the administration of vitamin D, and according to a subgroup study, a daily vitamin D supplement containing more than 2,000 IU significantly slowed the development of synovial tissue. Conclusion: Vitamin D supplementation did benefit those suffering from knee discomfort and knee dysfunction. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332033, identifier: CRD42022332033.

Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review.

Neuropathy in surgical-related locations has received concerns after total hip arthroplasty (THA), while the contralateral intercostal nerve (ICN) injury has not been reported. A 25-year-old female patient with a body mass index (BMI) of 17.9 kg/m2 visited the orthopedic outpatient clinic with complaints of progressive left hip pain for 20 days. She was diagnosed with left end-stage hip osteoarthritis and developmental dysplasia of the bilateral hips after radiographs and a detailed history-taking. After painstaking consideration, a cementless THA with the standard posterolateral approach was performed under general anesthesia. The procedure was difficult but successful. Unexpectedly, the numbness and slight tingling in the skin of the right breast, lateral chest wall, and axilla cropped up on the first postoperative day. Following the clinical features and the conclusion of the multidisciplinary discussion, we assume that ICN neuropathy is the diagnosis in this case due to compression of the lateral decubitus position during the operation. Her symptoms completely disappeared after using mecobalamin injection (0.5 mg, intramuscular injection, every other day) for 11 days. The Harris left hip score improved from 39 to 94, and the visual analogue scale from 7 was reduced to 2 on the day of discharge. There were no other complications within the first year after the operation. For THA, we should pay attention to some unexpected complications by virtue of the special position, especially in thin and low-BMI people, which suggested that further comprehensive perioperative nursing measures and the beneficial surgical position and anesthesia type were called for.

N6-methyladenine regulator-mediated RNA methylation modification patterns in immune microenvironment regulation of osteoarthritis.

Background: Osteoarthritis is a common chronic degenerative disease, and recently, an increasing number of studies have shown that immunity plays an important role in the progression of osteoarthritis, which is exacerbated by local inflammation. The role of N6-methyladenine (m6A) modification in immunity is being explored. However, the role of m6A modification in regulating the immune microenvironment of osteoarthritis remains unknown. In this study, we sought to discuss the association between the N6-methyladenine (m6A) modification and the immune microenvironment of osteoarthritis. Methods: First, the data and gene expression profiles of 139 samples, including 33 healthy samples and 106 osteoarthritis samples, were obtained from the Genetics osteoARthritis and Progression (GARP) study. Then the differences in m6A regulators between healthy individuals and osteoarthritis patients were analyzed. The correlation between m6A regulators and immune characteristics was also investigated by single-sample gene set enrichment analysis (ssGSEA). Principal component analysis (PCA), Gene Set Variation Analysis (GSVA) enrichment analysis, weighted gene coexpression network analysis (WGCNA), and Associated R packages were used to identify the m6A phenotype and its biological functions. Results: A total of 23 m6A regulators were involved in this study. We found a close correlation between most m6A regulators in all samples as well as in osteoarthritis samples. VIRMA and LRPPRC were the most highly correlated m6A regulators and showed a positive correlation, whereas VIRMA and RBM15B were the most negatively correlated. M6A regulators are associated with osteoarthritis immune characteristics. For example, MDSC cell abundance was strongly correlated with RBM15B and HNRNPC. Meanwhile, RBM15B and HNRNPC were important effectors of natural killer cell immune responses. IGFBP3 is an important regulator of cytolytic activity immune function. We performed an unsupervised consensus cluster analysis of the osteoarthritis samples based on the expression of 23 m6A regulators. Three different m6A subtypes of osteoarthritis were identified, including 27 samples in subtype C1, 21 samples in subtype C2, and 58 samples in subtype C3. Different m6A subtypes have unique biological pathways and play different roles in the immune microenvironment of osteoarthritis. Conclusion: The m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment in osteoarthritis.

Assessment of the effectiveness and satisfaction of platelet-rich plasma compared with hyaluronic acid in knee osteoarthritis at minimum 7-year follow-up: A post hoc analysis of a randomized controlled trial.

Background: Knee osteoarthritis (KOA) can be effectively treated conservatively using platelet-rich plasma (PRP) injections into the affected joints. While the short-term therapeutic clinical benefits were well documented, the mid-term results remain undetermined. To clarify its efficacy, the mid-term clinical outcomes of intra-articular injections of either PRP or hyaluronic acid (HA) in KOA were compared. Methods: One hundred patients who complied with the inclusion criteria were randomized to undergo once a week 3 weeks, intra-articular injections of either PRP or HA. Patients were evaluated before the injection, at 3, 6, and a mean of 78.9 months of follow-up. Eighty-five patients reached the final evaluation. Data on survival, re-intervention, pain, function, imaging, and satisfaction were collected and analyzed. Results: With surgery for any reason as the endpoint, the cumulative survival rate of the PRP group was 90%, while that of the HA group was 74%. There was a significant difference between the two groups in the total re-intervention rate (56.7% vs 16.2%, p < 0.05). The comparative analyses showed significant intergroup differences in the visual analog scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) (p < 0.01, p < 0.05, respectively) at the final follow-up. And base on the regression analyses, the type of treatment, age, and Kellgren-Lawrence (K-L) grade served as statistically an independent determinants of VAS (p < 0.001, p = 0.034, p < 0.001, respectively). Likewise, those variables independently determined WOMAC in our study. However, no difference was observed in the imaging evaluation, containing the K-L grade and Cartilage Lesion Score, between the two groups (p > 0.05). Besides, the satisfaction treated by the PRP was 78.6%, with a superiority compared with HA (55.8%, p < 0.05), and no complications were noted in the whole treatment process among patients who participated. Conclusion: PRP was more effective than HA in survival and re-intervention rates, VAS, and WOMAC, although there were no significant differences in the imaging evaluation between the two groups. Furthermore, patients treated with PRP were associated with higher satisfaction compared with HA.

Case report: Directional infusion of peripheral blood stem cells into the necrotic zone in femoral heads through the medial circumflex femoral artery: A tracing study.

Objective: This study aimed to explore whether peripheral blood stem cells (PBSCs) infused through the medial circumflex femoral artery to treat osteonecrosis of the femoral head (ONFH) could migrate into the necrotic area of femoral head. Methods: We collected PBSCs from a patient who had bilateral ONFH by apheresis technique using COBE spectra apheresis system (COBE BCT Inc, Lakewood, CO, USA) after subcutaneous injections of granulocyte-colony stimulating factor (G-CSF) at a dosage of 10 µg/kg for 4 days to mobilize PBSCs. After that, 100 MBq 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) was used to label PBSCs. 18F-FDG labeled PBSCs were infused into the left femoral head via the medial circumflex femoral artery to treat ONFH. Then the patient was underwent three-dimensional positron emission tomography (3D-PET) examination 60 min after cell infusion to monitor the biological distribution of 18F-FDG-labeled PBSCs, and to observe whether the transplanted PBSCs could migrate into the necrotic area of femoral head. Results: The total number of monouclear cells in the peripheral blood stem cell suspension was 1.95 × 108 which contained 2.20 × 106 CD34+ cells. The activity of 18F-FDG in the labeled cells was 1.8Bq/103 monouclear cells. 3D-PET imaging showed that 18F-FDG radioactivity was detected in the necrotic area of femoral head, acetabulum and femoral bone marrow cavity after transplantation of 18F-FDG-labeled PBSCs via the medial circumflex femoral artery. It is worth noting that although PBSCs labeled with 18F-FDG were widely distributed around the hip, such as femoral bone marrow cavity, femoral head and acetabulum, PBSCs were generally located in the necrotic area of femoral head. Conclusions: PBSCs could enter into the femoral head and migrate into the necrotic field of femoral head participating in the repair of osteonecrosis after infusion through the medial circumflex femoral artery.

Exploring the mechanism of Buyang Huanwu decoction in the treatment of lumbar disc herniation based on network pharmacology and molecular docking.

Buyang Huanwu decoction (BYHWD), as one of the traditional Chinese medicine formulas, is widely used in the clinical treatment of lumbar disc herniation (LDH) with curative effect. It has the characteristics of multi-component, multi-target, and mutual synergy, but the mechanism of action is often unclear. It needs some research to explore the molecular mechanism of BYHWD in the treatment of LDH based on network pharmacology and molecular docking. Screen the active compounds of BYHWD and predict drug-related gene/protein targets, which could determine the specific target of BYHWD in the treatment of LDH. Construct the "Drugs-Compounds-Targets" network and search for the core targets. Use Gene Ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking verification to explore the possible molecular mechanism. Eighty-two effective compounds and 666 targets of BYHWD, 187 targets for LDH treatment, and 20 core candidate targets were excavated. A total of 3414 entries were identified by Gene Ontology enrichment analysis, 173 related signal pathways were identified by Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and 5 core compounds were identified by molecular docking, which had a good affinity with core genes STAT3, JUN, AKT1, MAPK1, RELA, and PIK3CA. BYHWD may play the role of analgesic and improving function by synergistic anti-inflammatory and analgesic compounds, regulating cell metabolic differentiation, regulating immunity, and anticoagulation. BYHWD in the treatment of LDH may play a role in analgesia and improve function through multiple signaling pathways, including PI3K-Akt, mitogen-activated protein kinase, tumor necrosis factor, and interleukin-17. The PI3K-Akt signaling may be one of the key mechanisms.

Total knee arthroplasty in Ranawat II valgus deformity with enlarged femoral valgus cut angle: A new technique to achieve balanced gap.

BACKGROUND: Nearly 10% of patients undergoing primary total knee arthroplasty (TKA) have valgus deformity (VD) of the knee. For severe VD of the knee, a more lateral structural release is needed to achieve balance between medial and lateral space and neutral femorotibial mechanical axis (FTMA), which is challenging and technical. AIM: To introduce a new surgical technique of resection, soft tissue release, and FTMA for Ranawat type-II VD with a 5-year follow-up. METHODS: A retrospective study was conducted on patients who underwent TKA from December 2011 to December 2014. Hip-knee-ankle (HKA), range of motion (ROM), Oxford knee score (OKS), and knee society score (KSS) were used to assess the joint activity of patients in the new theory TKA group (NT-TKA) and were compared with those of the conventional TKA group (C-TKA). RESULTS: A total of 103 people (103 knees) were included in this study, including 42 patients with an average follow-up period of 83 mo in the C-TKA group and 61 patients with an average follow-up period of 76 mo in the NT-TKA group. Six patients had constrained prosthesis, one had common peroneal nerve injury, and two had joint instability in the C-TKA group, but none of these occurred in the NT-TKA group. There were significant statistical differences in constrained prosthesis usage and complications between the groups (P = 0.002 and P = 0.034, respectively). The KSS at 1 mo post-operation for the C-TKA and NT-TKA groups were 11.2 ± 3.8 and 13.3 ± 2.9, respectively, with a significant difference (P = 0.007). However, the data of HKA, ROM, OKS KSS, and prosthesis survival rate were insignificant (P > 0.05) in both the preoperative and follow-up periods. CONCLUSION: Adopting 5°-7° valgus cut angle for VD and sacrificing 2° neutral FTMA for severe VD which cannot be completely corrected during TKA can reduce the need for soft tissue release, maintain early joint stability, reduce the use of constrained prostheses, and minimize postoperative complications.

Total knee arthroplasty in patients with haemophilic arthropathy is effective and safe according to the outcomes at a mid-term follow-up.

BACKGROUND: Haemophilic arthropathy (HA), a common complication of haemophilia, is secondary to recurrent joint bleeding and increases the prevalence of end-stage osteoarthritis (OA). Total knee arthroplasty (TKA) is a reliable treatment for haemophilia patients. This study was performed to evaluate the mid-term outcomes of TKA for end-stage HA. We hypothesized that the rate of complications of TKA is higher for patients with haemophilia than for patients without haemophilia. METHODS: Patients with HA undergoing TKA from January 2015 to December 2016 in our centre were retrospectively reviewed. All patients were managed by a multidisciplinary team. The improvements in flexion contracture, range of motion (ROM), Knee Society Score (KSS; clinical and functional), Visual Analogue Scale (VAS) score, and satisfaction at final follow-up were analysed to evaluate the effectiveness of TKA in HA. The complications were analysed to evaluate the safety of TKA in HA. RESULTS: Twenty-eight patients (32 knees) were included in the study. The follow-up was 69.1 ± 5.1 months. Significant differences between the preoperative and final follow-up values of flexion contracture (which changed from 21.1 ± 6.5° to 14.3 ± 4.1°, P < 0.001), ROM (from 53.9 ± 15.0° to 70.3 ± 16.3°, P < 0.001), clinical KSS (from 33.5 ± 14.4° to 62.7 ± 9.5°, P < 0.001), functional KSS (from 46.1 ± 15.5° to 62.9 ± 9.7°, P < 0.001), and VAS score (from 6.8 ± 1.4 to 4.9 ± 1.3, P < 0.01) were observed. Importantly, the incidence of complications was 15.6% and the satisfaction was 100% in our mid-term study. CONCLUSION: Under elaborative and comprehensive management, TKA is effective and safe in patients with advanced HA on the basis of mid-term follow-up outcomes.

Intra-Articular Injection of Adipose-Derived Stem Cells Ameliorates Pain and Cartilage Anabolism/Catabolism in Osteoarthritis: Preclinical and Clinical Evidences.

Background: Osteoarthritis (OA) is the most common joint disorder, lacking disease-modifying treatments. Adipose-derived mesenchymal stem cells (ADSCs) are adult multipotent stromal cells obtained from fat tissue, which holds great potential in treating OA. This study aimed to evaluate the anti-OA efficacy of ADSCs from preclinical and clinical facets and explore the underlying mechanism of action. Methods: In vivo, a single dose of 5 × 105 ADSCs was injected into the knee joints of monoiodoacetate-induced OA rat model. The levels of metabolic and hypertrophic molecules (MMP13, Collagen II, Collagen X) of chondrocytes were measured by immunohistochemistry. In vitro, cell viability assay was conducted to detect the proliferation ability of chondrocytes treated with ADSCs conditioned medium (ADSCs-CM). Quantitative real-time polymerase chain reaction and Western blot assays were applied to explore the mechanism of action of ADSCs. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of ADSCs on OA patients. Results: The animal study showed that ADSCs significantly alleviated OA cartilage lesions in rats, as was confirmed by downregulation of the MMP13 and Collagen X and upregulation of the Collagen II. In vitro data showed that ADSCs-CM promoted the proliferation of chondrocytes, and significantly restored the IL-1ß-induced abnormal expressions of molecular markers IL-6, Aggrecan, MMP3, MMP13, Collagen II, Collagen X, ADAMTS5, ADAMTS9, SOX6, and SOX9 in chondrocytes. Such regulatory effects of ADSCs-CM on the proliferation and these anabolic, catabolic, and hypertrophic markers of chondrocytes suggested a paracrine-based mode of action of ADSCs. Furthermore, the clinical data showed that ADSCs reduced pain and repaired cartilage damage in OA patients, with no adverse events. Conclusion: This study demonstrated the anti-OA efficacy, safety, and a paracrine-based mechanism of ADSCs, providing a promising cell-based therapeutic option for OA treatment.

Col9a2 gene deletion accelerates the degeneration of intervertebral discs.

As an essential component of the extracellular matrix (ECM) in cartilage, the α2 chain of type IX collagen (Col9a2), has been implicated in human intervertebral disc degeneration (IVDD). However, the precise role of the Col9a2 gene in the pathogenesis of IVDD has remained elusive. In the present study, the spines of Col9a2-deficient (Col9a2-/-) mice were systematically analyzed and compared with wild-type control mice using micro-CT (µCT), histomorphology, immunofluorescence, immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR). µCT analysis revealed that endplate (EP) osteochondral remodeling in the Col9a2-/- group was accompanied by a significant increase in EP porosity. Likewise, histopathological staining at 12 weeks revealed that the Col9a2-/- mice exhibited a marked early-stage IVDD phenotype, including EP sclerosis, calcification and annulus fibrosus rupture. The immunofluorescence results indicated that Col9a2 was extensively expressed in the IVDs, whereas it was barely detectable in Col9a2-/- mice. Immunohistochemical and RT-qPCR analyses demonstrated that the expression levels of Col2a1 and Aggrecan in the IVDs of Col9a2-/- mice were significantly decreased. In addition, the levels of Mmp13, ADAM metallopeptidase with thrombospondin type 1 motif 5, Col10a1 and Runx family transcription factor 2 were significantly elevated. These results suggested that deletion of the Col9a2 gene led to osteochondral remodeling of cartilage EP and suppressed ECM synthesis, accelerating matrix degradation and chondrocyte hypertrophy in the IVD tissue.

Quercetin mediates TSC2-RHEB-mTOR pathway to regulate chondrocytes autophagy in knee osteoarthritis.

OBJECTIVE: This study aimed to explore the specific molecular mechanism of the therapeutic effect of quercetin in knee osteoarthritis (KOA). METHODS: The KOA rat model was constructed by excising the medial meniscus and transecting the anterior meniscus. Joint injuries in rats were determined by Hematoxylin-Eosin (H&E) and Safranin O staining. The severity of KOA was then assessed according to the Osteoarthritis Research Society International (OARSI). The expressions of TSC2 and LC2B in joint tissue were measured by immunohistochemistry. Besides, chondrocytes treated with 10 ng/ml IL-1ß were used to construct a chondrocyte arthritis model, while those treated with 4 or 8 µM quercetin were served as treatment groups. MTT, flow cytometry and toluidine blue staining were used to detect cell viability, apoptosis and mucopolysaccharide synthesis, respectively. qRT-PCR or Western blot was performed to determine the expressions of MMP-13, collagen II, Aggrecan, TSC2, RHEB, mTOR, p-mTOR, ULK1, p-ULK1, LC3B-I, LC3B-II and P62 in chondrocytes. RESULTS: Quercetin alleviated the joint injury and suppressed the increase in MMP-13 expression and the decreases in collagen II and Aggrecan expressions in KOA rats. In addition, quercetin suppressed RHEB, p-mTOR, p-ULK1 and P62 expressions but promoted TSC2 and LC3BII expressions in KOA rats. Furthermore, quercetin could relieve the decrease of cell viability and the increase of apoptosis that induced by IL-1ß, and promote the synthesis of IL-1ß-inhibited mucopolysaccharide in chondrocytes. Nevertheless, siTSC2 partially offset the therapeutic effects of quercetin in chondrocytes. CONCLUSION: Quercetin alleviated KOA by mediating the TSC2-RHBE-mTOR signaling pathway.

Total knee arthroplasty and femoral osteotomy with a patient-specific cutting guide to treat haemophilic arthritis with severe extra-articular deformity: A case report and review of literatures.

Background: Total knee arthroplasty (TKA) is recommended for haemophilic patients with end-stage arthritis. TKA combined with a one-stage extraarticular osteotomy is uncommon in the treatment of haemophilic arthritis (HA) with severe extra-articular deformities (EADs) and a history of inhibitors under the guidance of a patient-specific cutting guide (PSI). Case presentation: We reported a 20-year-old male patient with severe haemophilia, limited knee functionality, a 30° sagittal deformity on the femoral side and a history of inhibitors. We adopted the Van Creveld protocol to decrease the inhibitors. TKA and extra-articular osteotomy (EAO) were performed simultaneously and sequentially under the guidance of PSI. An appropriate central alignment of the lower limb was restored by using cement prostheses with antibiotics and femur shaft locking compression plates. The last follow-up showed that the knee function was good, the VAS score was 0, the WOMAC score was 18 and the ROM was 0°-95°. Conclision: Regular haematology management can reduce the perioperative bleeding risk in haemophilic patients treated with inhibitors. PSI plays an important role in guiding the TKA and EAO of end-stage HA patients with severe EAD.

Fractions of Shen-Sui-Tong-Zhi Formula Enhance Osteogenesis Via Activation of ß-Catenin Signaling in Growth Plate Chondrocytes.

Background: Shen-sui-tong-zhi formula (SSTZF) has been used to treat osteoporosis for decades and shows excellent clinical efficacy. This article aims to explore the optimal anti-osteoporotic ingredient and its precise mechanisms in mice models. Methods: In this study, we first screened the optimal anti-osteoporosis fraction of SSTZF extract in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old female C57BL/6J mice were administrated with each fraction of SSTZF. At 10 weeks after ovariectomy (OVX), femurs were collected for tissue analyses, including histology, micro-CT, biomechanical tests, and immunohistochemistry for ALP, FABP4, and ß-catenin. Additionally, we also evaluated the mRNA expression level of ALP and FABP4 and the protein expression level of ß-catenin after being treated with SSTZF extract in C3H10T1/2 cells. Moreover, we investigated the anti-osteoporosis effect of SSTZF extract on mice with ß-catenin conditional knockout in growth plate chondrocytes (ß-catenin Gli1ER mice) through µCT, histology, and immunohistochemistry analyzes. Results: At 10 weeks after treatment, osteoporosis-like phenotype were significantly ameliorated in SSTZF n-butanol extract (SSTZF-NB) group mice, as indicated by increased trabecular bone area and ALP content, and decreased lipid droplet area and FABP4 content. No such improvements were observed after being treated with other extracts, demonstrating that SSTZF-NB is the optimal anti-osteoporosis fraction. Additionally, the elevated ß-catenin was revealed in both OVX mice and C3H10T1/2 cells with SSTZF-NB administered. Furthermore, a significant osteoporosis-like phenotype was observed in ß-catenin Gli1ER mice as expected. However, SSTZF-NB failed to rescue the deterioration in ß-catenin Gli1ER mice, no significant re-upregulated ALP and downregulated FABP4 were observed after being treated with SSTZF-NB, demonstrating that SSTZF-NB prevents bone loss mainly via ß-catenin signaling. Conclusion: SSTZF-NB enhances osteogenesis mainly via activation of ß-catenin signaling in growth plate chondrocytes. SSTZF-NB is the optimal anti-osteoporosis fraction of SSTZF and it can be considered a salutary alternative therapeutic option for osteoporosis.