BACKGROUND: Studies comparing the effectiveness of arthroscopic knee surgery and conservative treatment on knee osteoarthritis (OA) came up with inconsistent results. Systematic review on this topic still is still lacking. This systematic review and meta-analysis aimed to evaluate the effectiveness of arthroscopic knee surgery on knee OA, compared to conservative treatments.
METHODS: Literature searches were performed in PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) published before on 1st July 2024. Studies comparing the effectiveness of arthroscopy and conservative treatments only on knee OA were included. Quality of included studies was evaluated by risk of bias 2 (ROB2). Long-term results in terms of pain relief, functional recovery and patients reported satisfaction were meta-analyzed to evaluate the therapeutic effectiveness.
RESULTS: Ten studies were included in this review, among which only 1 was considered as low risk of bias. Five studies were involved in meta-analyses and no difference was found in therapeutic effectiveness of arthroscopic surgery and conservative treatment on knee OA, in the evaluation of VAS (p = 0.63), WOMAC (p = 0.38), SF-36 (p = 0.74) and patient satisfaction (p = 0.07).
CONCLUSIONS: The evidence does not support the effectiveness of arthroscopic knee surgery compared to conservative treatments in knee OA.

UNASSIGNED: The purpose of this study was to evaluate the relationship between the joint line convergence angle (JLCA) and the severity of medial knee osteoarthritis (OA). We hypothesise that JLCA is the most associated factor with the severity of medial knee OA.
UNASSIGNED: This retrospective study included a total of 202 knees that underwent either high tibial osteotomy or medial meniscus repair/partial resection. Kellgren-Lawrence grade and hip-knee-ankle angle (HKAA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA) and JLCA were assessed from preoperative radiographs. Medial meniscus extrusion (MME) was measured using preoperative magnetic resonance imaging. The International Cartilage Research Society (ICRS) grade on the medial femoral condyle and medial tibial plateau were also assessed. The relationships between JLCA and Kellgren-Lawrence grades and MME and ICRS grades were analysed using Spearman\'s correlation test and regression analysis.
UNASSIGNED: The JLCA was correlated with the Kellgren-Lawrence grade (R = 0.765, p < 0.001), MME (R = 0.638, p < 0.001), ICRS grade on the MFC (R = 0.586, p < 0.001) and the MTP (R = 0.586, p < 0.001). Regression analysis showed that age (p = 0.002) and JLCA (p < 0.001) were associated with Kellgren-Lawrence grade. Furthermore, JLCA was related to ICRS grade on the MFC (p < 0.001) and MTP (p < 0.001).
UNASSIGNED: The JLCA, reflecting radiological severity, meniscus status, and cartilage lesion, was the most associated alignment parameter in the severity of medial knee OA. The JLCA may be beneficial for quantitative assessment of medial knee OA.
UNASSIGNED: Level III, retrospective cohort study.

BACKGROUND: Cartilage metabolism dysregulation is a crucial driver in knee osteoarthritis (KOA). Modulating the homeostasis can mitigate the cartilage degeneration in KOA. Curcumenol, derived from traditional Chinese medicine Curcuma Longa L., has demonstrated potential in enhancing chondrocyte proliferation and reducing apoptosis. However, the specific mechanism of Curcumenol in treating KOA remains unclear. This study aimed to demonstrate the molecular mechanism of Curcumenol in treating KOA based on the transcriptomics and metabolomics, and both in vivo and in vitro experimental validations.
METHODS: In this study, a destabilization medial meniscus (DMM)-induced KOA mouse model was established. And the mice were intraperitoneally injected with Curcumenol at 4 and 8 mg/kg concentrations. The effects of Curcumenol on KOA cartilage and subchondral was evaluated using micro-CT, histopathology, and immunohistochemistry (IHC). In vitro, OA chondrocytes were induced with 10 μg/mL lipopolysaccharide (LPS) and treated with Curcumenol to evaluate the proliferation, apoptosis, and extracellular matrix (ECM) metabolism through CCK8 assay, flow cytometry, and chondrocyte staining. Furthermore, transcriptomics and metabolomics were utilized to identify differentially expressed genes (DEGs) and metabolites. Finally, integrating multi-omics analysis, virtual molecular docking (VMD), and molecular dynamics simulation (MDS), IHC, immunofluorescence (IF), PCR, and Western blot (WB) validation were conducted to elucidate the mechanism by which Curcumenol ameliorates KOA cartilage degeneration.
RESULTS: Curcumenol ameliorated cartilage destruction and subchondral bone loss in KOA mice, promoted cartilage repair, upregulated the expression of COL2 while downregulated MMP3, and improved ECM synthesis metabolism. Additionally, Curcumenol also alleviated the damage of LPS on the proliferation activity and suppressed apoptosis, promoted ECM synthesis. Transcriptomic analysis combined with weighted gene co-expression network analysis (WGCNA) identified a significant downregulation of 19 key genes in KOA. Metabolomic profiling showed that Curcumenol downregulates the expression of d-Alanyl-d-alanine, 17a-Estradiol, Glutathione, and Succinic acid, while upregulating Sterculic acid and Azelaic acid. The integrated multi-omics analysis suggested that Curcumenol targeted KDM6B to regulate downstream protein H3K27me3 expression, which inhibited methylation at the histone H3K27, consequently reducing Succinic acid levels and improving KOA cartilage metabolism homeostasis. Finally, both in vivo and in vitro findings indicated that Curcumenol upregulated KDM6B, suppressed H3K27me3 expression, and stimulated collagen II expression and ECM synthesis, thus maintaining cartilage metabolism homeostasis and alleviating KOA cartilage degeneration.
CONCLUSIONS: Curcumenol promotes cartilage repair and ameliorates cartilage degeneration in KOA by upregulating KDM6B expression, thereby reducing H3K27 methylation and downregulating Succinic Acid, restoring metabolic stability and ECM synthesis.

Background: Osteoarthritis is a chronic disorder that affects the synovial joints by the progressive loss of articular cartilage. In the hip, the largest weight-bearing joint, the deterioration of articular cartilage and acetabular labrum can cause pain, diminishing the quality of life for patients. This study presents changes in reported pain scales from patients who received Wharton\'s jelly applications to cartilage deterioration in the hip from the observational retrospective repository at Regenative Labs. Methods: Sixty-nine patients were selected based on inclusion criteria with patient-reported pain scales, including the Numeric Pain Rating Scale and the Western Ontario and McMaster University Osteoarthritis Index, collected at the initial application, 30, and 90-day follow-up visits. Thirteen patients received a second allograft application and had additional follow-up visits at 120 and 180 days. Results: Five of the six scales used showed a statistically significant improvement in average scores across the cohort. The greatest improvements were observed in the NPRS with a 31.36% improvement after 90 days and a 44.64% improvement for patients with two applications after 180 days. The minimal clinically important difference (MCID) was also calculated to determine the perceived value of care for each patient with 44.9% of patients exceeding the MCID and 78.3% reporting at least one level of improvement. Conclusions: The positive outcomes for the patients in this cohort suggest WJ to be a promising alternative care option for patients with structural tissue degeneration in the hip refractory to the current standard of care.

The objectives of this study were to evaluate the reliability of cartilage T2 relaxation time measurements and to identify focal changes in T2 relaxation on the affected knee from 6 to 24 months after anatomic anterior cruciate ligament reconstruction (ACLR). Data from 41 patients who received anatomic ACLR were analyzed. A bilateral 3.0-T MRI was acquired 6 and 24 months after ACLR. T2 relaxation time was measured in subregions of the femoral condyle and the tibial plateau. The root-mean-square coefficient of variation (RMSCV) was calculated to evaluate the reliability of T2 relaxation time in the contralateral knee. Subregion changes in the affected knee T2 relaxation time were identified using the contralateral knee as a reference. The superficial and full thickness layers of the central and inner regions showed good reliability. Conversely, the outer regions on the femoral side and regions in the deep layers showed poor reliability. T2 relaxation time increased in only 3 regions on the affected knee when controlling for changes in the contralateral knee, while changes in T2 relaxation time were identified in 14 regions when not using the contralateral knee as a reference. In conclusion, evaluation of cartilage degeneration by T2 relaxation time after ACLR is most reliable for central and inner cartilage regions. Cartilage degeneration occurs in the central and outer regions of the lateral femoral condyle from 6 to 24 months after anatomic ACLR.

OBJECTIVE: To explore the feasibility of Ultra-short echo time (UTE) - MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis.
METHODS: Twenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained.
RESULTS: 91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = -0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = -0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, -0.652, -0.518, p < 0.001, respectively).
CONCLUSIONS: UTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively.
UNASSIGNED: Ultra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration.
CONCLUSIONS: Conventional MR may miss some early cartilage changes due to relatively long echo times. Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo. UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.

OBJECTIVE: Quantitative MRI techniques such as T2 mapping are useful in comprehensive evaluation of various pathologies of the knee joint yet require separate scans to conventional morphological measurements and long acquisition times. The recently introduced 3D MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with Intuitive Relaxometry) technique can obtain simultaneous morphologic and quantitative information of the knee joint. To compare MIXTURE with conventional methods and to identify differences in morphological and quantitative information.
METHODS: Phantom studies were conducted, and in vivo human scans were performed (20 patients) presented with knee arthralgia. MIXTURE is based on 3D TSE without and with T2 preparation modules in an interleaved manner for both morphology with PDW and fat suppressed T2W imaging as well as quantitative T2 mapping within one single scan. Image quality and lesion depiction were visually assessed and compared between MIXTURE and conventional 2D TSE by two experienced radiologists. Contrast-to-noise ratio was used to assess the adjacent tissue contrast in a quantitative way for both obtained PDW and fat suppressed T2W images. Quantitative T2 values were measured in phantom and from in vivo knee cartilage.
RESULTS: The overall diagnostic confidence and contrast-to-noise ratio were deemed comparable between MIXTURE and 2D TSE. While the chosen T2 preparation modules for MIXTURE rendered consistent T2 values comparing to the current standard, measured cartilage T2 values ranged from 26.1 to 50.7 ms, with significant difference between the lesion and normal areas (p < 0.05).
CONCLUSIONS: MIXTURE can help to provide high-resolution information for both anatomical and pathological assessment.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. β-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of β-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism.
METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and β-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis.
RESULTS: The loss of β-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1β) factors in condylar cartilage were increased in β-arrestin2 null mice compared with WT mice. Moreover, the loss of β-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA.
CONCLUSIONS: In conclusion, we demonstrated for the first time that β-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, β-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

From the perspective of lncRNA MALAT1 regulating cholesterol metabolism in chondrocytes, this paper explores the effect and mechanism of Tougu Xiaotong Capsules(TGXTC) in delaying the degeneration of osteoarthritis. After one week of adaptive feeding, 48(8-week-old) C57BL/6 mice were randomly divided into a blank group(12 mice) and a model group(36 mice) by random number table method. The mice in the model group were anesthetized by inhalation of 5% isoflurane, and the OA model was induced by Hulth method. The experiment randomly divided the mice into a model group(12 mice), a drug-positive group(taururso-deoxycholic acid)(12 mice), and a TGXTC group(12 mice). The drug-positive group was given 500 mg·kg~(-1) taurodeoxycholic acid by intragastric administration. TGXTC group was given TGXTC 368 mg·kg~(-1) by gavage. The blank group and model group were given the same amount of normal saline for four weeks. After the intervention, the mice in each group were killed under anesthesia, and the knee cartilage tissue was separated and collected. The morphologic changes of knee cartilage were observed. The level of lncRNA MALAT1 in the cartilage tissue was detected by real-time PCR. The protein expressions of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in mouse articular cartilage were detected by Western blot. Lentivirus-coated plasmid was used to transfect mouse chondrocytes with sh-MALAT1. The gene levels of lncRNA MALAT1 in mouse chondrocytes transfected with sh-MALAT1 were detected by real-time PCR. Western blot was used to detect the effect of TGXTC on the protein content of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in thapsigargin(TG)-induced mouse chondrocytes after lncRNA MALAT1 knockdown. Flow cytometry was used to detect the effect of TGXTC on apoptosis of TG-induced mouse chondrocytes after lncRNA MALAT1 knockdown. The results of HE and saffranine O staining showed that compared with the model group, the structure of the cartilage layer was basically intact; the damage degree of joint structure was significantly improved, and the cartilage matrix was significantly enhanced by saffranine O staining in the TGXTC group and drug-positive group. Compared with the model group, the lncRNA MALAT1 level was significantly decreased in the TGXTC group and drug-positive group. Compared with the model group, the protein content of ABCA1, ApoA1, and LXRβ was significantly increased, while that of CHOP and caspase-3 in the TGXTC group and drug-positive group significantly decreased. Compared with the TG group, the lncRNA MALAT1 level in the TG+sh-MALAT1 group was decreased. The lncRNA MALAT1 level in the TG+sh-MA-LAT1+TGXTC group was increased compared with the TG+TGXTC group. Western blot results showed that compared with the model group, protein expressions of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in the TGXTC group were significantly decreased, after lncRNA MALAT1 knockdown, the regulation and apoptosis of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in TG-induced mouse chondrocytes were weakened by TGXTC. TGXTC can improve the disorder of cholesterol metabolism in OA chondrocytes and delay OA degeneration, which is closely related to the regulation of lncRNA MALAT1.