Joint Osteoarthritis Research Articles

The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review.

Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.

Intra-articular pathologies detected by magnetic resonance imaging in patients with temporomandibular disorders undergone successful non-surgical treatments

ObjectiveThis study aimed to study on the MRI findings suggesting intra-articular pathologies in patients with temporomandibular disorders (TMD) undergone successful non-surgical treatments, and to discuss on their intra-articular pathological conditions with clinical symptoms. Patients and methodsOne-hundred eleven TMJs of the consecutive 80 TMD patients were enrolled in this study. These TMJs were classified into the following 3 Groups, Group I: Bilateral 62 TMJs of the 31 patients with masticatory-muscle (MM) symptoms without functional pain, Group II: Affected-side TMJs of the 31 patients with unilateral functional MM pain, Group III: Affected-side TMJs of the 18 patients with unilateral functional TMJ pain. The detection rates of joint effusion (JE), osteoarthritis (OA), and disc displacement (DD) on the MR images were investigated. The correlations of JE, OA, DD, age, and gender were also analyzed. ResultsIn each Group, the detection rates of JE, OA, and DD were more than 70%, and no findings of them were sometimes observed. The detection ratio of moderate/marked JE in Group II was significantly higher among the 3 Groups. The significant correlation of JE, OA, and DD was found, and that of OA and age was also observed. ConclusionsOur results suggest that intra-articular pathologies often occur even in the painless TMJs, and functional TMJ pain sometimes appear even in the TMJs with early-stage OA, which cannot be detected by MRI. Furthermore, the TMJ synovitis occurred in patients with functional MM pain may be more severe than that in the painful TMJ.

Culture of Hoffa fat pad mesenchymal stem/stromal cells on microcarrier suspension in vertical wheel bioreactor for extracellular vesicle production

BackgroundMesenchymal stromal cells (MSCs) are increasingly employed in regenerative medicine approaches for their immunomodulatory and anti-inflammatory properties, which are encoded in their secretome including extracellular vesicles (EVs). The Hoffa fat pad (HFP) located infrapatellarly harbours MSCs that could assist in tissue homeostasis in osteoarthritic joints. Intraarticular injection therapies based on blood products could modulate the populations of released HFP-MSC-EVs in a quantitative manner.MethodsTo obtain amounts of HFP-MSC-derived EVs that allow pre-clinical evaluation, suitable EV production systems need to be developed. This work investigates the release of EVs from primary HFP-MSCs cultivated in a 3D environment using microcarrier suspension culture in a vertical wheel bioreactor in comparison to conventional 2D culture. To simulate an intraarticular blood product therapy, cultures were treated with citrate-anticoagulated platelet-rich plasma (CPRP) or hyperacute serum (hypACT) before EV collection. HFP-MSC-EVs are enriched via ultrafiltration and characterised via Western Blot, nanoparticle tracking analysis in scatter as well as fluorescence mode. EV potency was determined via RT-qPCR analysing the expression of type II and X collagen (COL2 and COL10), as well as inducible nitric oxide synthase (iNOS) in primary OA chondrocytes.ResultsBlood product supplementation elevated HFP-MSC metabolic activity as determined via XTT assay over the course of 14 days. 3D culture resulted in a roughly 100-fold EV yield compared to 2D culture and elevated number of EVs released per cell. Total protein content correlated with the EV concentration. While typical EV marker proteins such as CD9, CD63 or Alix were detected in total protein extracts, CD9 and CD73 colocalised on individual EVs highlighting their cell origin. The type of blood product treatment did not affect the size or concentration of EVs obtained from HFP-MSCs. Assessing potency of 3D culture EVs in comparison to 2D EVs revealed superior biological activity with regard to inhibition of inflammation, inhibition of chondrocyte hypertrophy and induction of cartilage-specific ECM production.ConclusionsHFP-MSCs proliferate in presence of human blood products indicating that animal serum in culture media can be avoided in the future. The culture of HFP-MSCs in the employed bioreactor was successfully used to generate quantities of EVs that could allow evaluation of HFP-MSC-EV-mediated effects in pre-clinical settings. In addition, EV potency of 3D EVs is superior to EVs obtained in conventional 2D culture flasks.

Excellent 2-Year Outcomes of a Midlevel Constrained Liner Used in Stemless Primary TKA

Introduction: Instability after total knee arthroplasty (TKA) remains a leading cause of revision TKA and can lead to patient dissatisfaction. While many companies have developed midlevel constrained (MLC) polyethylene inserts in primary TKAs, there is little data on their outcomes. Purpose: We sought to analyze short-term outcomes including survivorship, rates of manipulation under anesthesia (MUA), and improvements in patient-reported outcome measures (PROMs) preoperatively to postoperatively in one design of MLC TKA. Methods: We prospectively followed consecutive primary TKA patients who received constrained inserts (Journey II or Legion Genesis II, Smith and Nephew) from 5 surgeons, 2019 to 2020, at a single academic institution. We analyzed revision-free survivorship, MUA rates, and PROMs, preoperatively to postoperatively. Results: A total of 356 patients were included with a mean age of 64 years; 49% were male and the mean body mass index (BMI) was 31 kg/m2. Sixteen patients (4.5%) underwent MUA and 3 patients (0.8%) underwent revision. Two patients underwent polyethylene exchange and patellar resection for patellar loosening. One patient underwent liner exchange for instability. The 2-year revision-free survivorship was 98.5% (95% confidence interval [CI]: 96.6%–100%). Survivorship free from revision for tibial or femoral aseptic loosening was 100% at 2 years. The 2-year survivorship free from MUA was 92.3% (95% CI: 88.6%–96.1%). The mean Knee Osteoarthritis and Injury Outcomes Score Joint Replacement (KOOS JR) was 81 at 2 years follow-up, while the Lower Extremity Activity Score (LEAS) score was 10.5. Conclusion: At a mean of 3 years follow-up, 2 types of MLCs used in primary TKA were associated with a low rate of early revision, low rate of MUA, and reliable improvement in functional outcomes. These MLCs were not associated with early loosening or unique failure modes.

The use of symptomatic slow-acting drugs for osteoarthritis of the joints of the hands: Accent on microcirculation parameters

The aim of the study – to evaluate the effectiveness of the drug Alflutop (bioactive concentrate of small marine fish), as well as its effect on microcirculation parameters in patients with osteoarthritis (OA) of small joints of the hands.Patients and methods. The study included 80 patients aged 35 to 65 years with OA of small joints of the hands, stage I– II according to Kellgren – Lawrence, with pain ≥40 mm and ≤90 mm on a visual analogue scale (VAS). Subjects were distributed in 1:1 ratio. In the study group (combined therapy) patients received Alflutop according to the standard scheme: 2 ml intramuscularly every other day N 10 and meloxicam 7.5–15 mg per day in the “on demand” mode. The second group (monotherapy) received meloxicam 7.5–15 mg per day N 20. During the observation, the dynamics of joint pain on the VAS scale, the dynamics of the disease on the VAS scale by the patient and the doctor, the functional Dreiser index and AUSCAN (Australian/Canadian Osteoarthritis Hand Index), nailfold capillaroscopy (NFC) with an assessment of the number of capillaries and the number of alterations per 1 mm of the distal row of capillaries were evaluated. The duration of the study was 6 weeks.Results and discussion. By the 35th day of treatment with Alflutop in combination with meloxicam, a statistically significant decrease in pain and functional activity of the disease was found according to the VAS indices, the AUSCAN index (p<0.05) compared with the meloxicam monotherapy group. Microcirculation parameters according to NFC data in the Alflutop and meloxicam group remained stable by the end of the study (p>0.05). In meloxicam monotherapy group, by the 35th day of follow-up, there was a significant increase in the number of altered capillaries by 1 mm of the distal row of the nail (p<0.001).Thus, Alflutop demonstrates clinical efficacy in OA of the joints of the hands (reduces pain, stiffness, improves joint function). In addition, the effect of Alflutop with respect to slowing down microcirculatory disorders is not excluded.

Characterisation and Expression of Osteogenic and Periodontal Markers of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) from Diabetic Knee Joints.

Type 2 diabetes mellitus (T2DM) represents a significant health problem globally and is linked to a number of complications such as cardiovascular disease, bone fragility and periodontitis. Autologous bone marrow mesenchymal stem cells (BM-MSCs) are a promising therapeutic approach for bone and periodontal regeneration; however, the effect of T2DM on the expression of osteogenic and periodontal markers in BM-MSCs is not fully established. Furthermore, the effect of the presence of comorbidities such as diabetes and osteoarthritis on BM-MSCs is also yet to be investigated. In the present study, BM-MSCs were isolated from osteoarthritic knee joints of diabetic and nondiabetic donors. Both cell groups were compared for their clonogenicity, proliferation rates, MSC enumeration and expression of surface markers. Formation of calcified deposits and expression of osteogenic and periodontal markers were assessed after 1, 2 and 3 weeks of basal and osteogenic culture. Diabetic and nondiabetic BM-MSCs showed similar clonogenic and growth potentials along with comparable numbers of MSCs. However, diabetic BM-MSCs displayed lower expression of periostin (POSTN) and cementum protein 1 (CEMP-1) at Wk3 osteogenic and Wk1 basal cultures, respectively. BM-MSCs from T2DM patients might be suitable candidates for stem cell-based therapeutics. However, further investigations into these cells' behaviours in vitro and in vivo under inflammatory environments and hyperglycaemic conditions are still required.

The use of resurfacing implants (CapFlex-PIP) for fingers proximal interphalangeal joint osteoarthritis: satisfactory clinical and radiological results at 5-year follow-up

The use of resurfacing implants (CapFlex-PIP) for fingers proximal interphalangeal joint osteoarthritis: satisfactory clinical and radiological results at 5-year follow-up

Arthroscopic distal clavicle resection versus conservation in patients with combined rotator cuff tears and acromioclavicular joint osteoarthritis.

The most common cause of shoulder pain originating from the acromioclavicular (AC) joint is osteoarthritis, causing pain and disability. Operative Management of AC arthritis includes arthroscopic distal clavicle resection (DCR) and open clavicle resection. This study was conducted to evaluate the outcomes of isolated rotator cuff repair with conservative treatment of ACJ arthritis versus the combined resection of the distal clavicle with the repair of a rotator cuff tear, in cases with acromioclavicular arthritis. A total of 46 patients with unilateral or bilateral combined rotator cuff tear and acromioclavicular arthritis were included, they were classified into 2 independent groups: Conservative group (23 patients), and DCR group (23 patients). All patients were subjected to full history taking, examination, pre and post-operative University of California at Los Angeles shoulder scoring scale (UCLA), Antero-Posterior and Zanca X-rays views, early and late complications. Mean age was (51 ± 9) years, males were predominant (56.5%). The average post-operative UCLA score was (31.1 ± 4.9), and the average time to return to work was (214 ± 22). (2.2%) of patients had early complications, (19.6%) had late complications, (32.6%) had > 24h till 1st post-operative analgesia, and (87%) needed MgSO4 Injection. We found a highly significant increase in UCLA score measurements in the Conservative group, and a highly significant increase in UCLA score measurements in the DCR group (p < 0.01). But there was no difference between the 2 groups. Conventional conservative approach with arthroscopic rotator cuff repair and subacromial decompression has proven to be as effective as arthroscopic rotator cuff repair and subacromial decompression with DCR, in terms of efficacy and safety profiles in short term, but with more risks of potential hazards and cost with the DCR.

Equine Models of Temporomandibular Joint Osteoarthritis: A Review of Feasibility, Biomarkers, and Molecular Signaling.

Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and imaging modalities that can be performed on horses, as well as easy tissue and synovial fluid collection. The morphological and functional similarities of TMJ structures in both species make the equine model of TMJ OA an excellent opportunity to track disease progression and response to treatment. However, much work remains to be carried out to determine the utility of human TMJ OA biomarkers in horses. Among the main TMJ OA biomarkers, IL-1, IL-6, TGF-β, TNF-α, and PGE2 have been recently investigated in the equine model. However, the majority of biomarkers for cartilage degradation, chondrocyte hypertrophy, angiogenesis, and TMJ overload-as well as any of the main signaling pathways-have not been studied so far. Therefore, it would be advisable to focus further research on equine specimens, considering both mediators and signaling.

The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms

Background: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. Hypothesis: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. Study Design: Controlled laboratory study. Methods: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography–tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. Results: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P≤ .0001) and docosahexaenoic acid (P≤ .0001) and the pro-resolving lipid mediators 17– and 14–hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P = .0019 and P≤ .0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9–, 11,12–, and 14,15–dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P = .0004, R2 = 0.251; P = .0002, R2 = 0.278; and P = .0012, R2 = 0.214, respectively). Conclusion: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. Clinical Relevance: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies.

Effects of endoplasmic reticulum stress on chondrocyte apoptosis via the PI3K/AKT signaling pathway

Chondrocytes undergo endoplasmic reticulum stress (ERS)-induced apoptosis under abnormal stimulation. However, the underlying molecular mechanism remains unclear. We investigated the regulatory effect of the PI3K/AKT signaling pathway on ERS and its effect on chondrocyte apoptosis. In addition, we established a unilateral anterior crossbite (UAC) model in rats to induce temporomandibular joint osteoarthritis (TMJOA). Chondrocytes were isolated from the temporomandibular joints and treated with lipopolysaccharide (LPS) in vitro. Protein expression of ERS and apoptosis markers (GRP78 and CASP12) was analyzed by immunohistochemistry and western blotting. The expression of GRP78, CASP12, p-PI3K, and p-AKT significantly increased in the UAC group. LY294002, a PI3K/AKT signaling pathway inhibitor, reduced the protein expression of GRP78, ATF4, CHOP, and CASP12, whereas 740 Y-P, an activation agent, elevated the expression of proteins GRP78, ATF4, CHOP, and CASP12. In the present study, UAC and LPS stimulation induced apoptosis of chondrocytes in the ERS pathway. Inhibition of the PI3K/AKT signaling pathway reduced ERS-induced chondrocyte apoptosis.

Sex dependent differences of temporomandibular condylar bone mineral density distribution

ABSTRACT Objective The objective of this study was to examine whether bone mineral density (BMD) distribution in the mandibular condyle and facial morphology are associated with temporomandibular joint osteoarthritis (TMJ OA) using clinical cone beam computed tomography (CBCT) images. Methods CBCT images of 35 adults (16 male and 19 female) were examined to obtain TMJ OA counts, cephalometric analyses, and histograms of gray values that are proportional to BMD. Mean, standard deviation (SD), and low and high gray values at the 5th and 95th percentiles (Low5 and High5) of the histograms were measured. Results The female group had significantly higher values of TMJ OA counts, mean, and SD on the right mandibular condyle, High5 on both sides, and all gray value parameters for total (right + left) than the male group. Conclusion Comprehensive analysis of BMD distribution in the mandibular condyle can provide useful information for prognosis of TMJ OA.

MiR-708–5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway

ObjectiveAgeing and aberrant biomechanical stimulation are two major risk factors for osteoarthritis (OA). One of the main characteristics of aged cartilage is cellular senescence. One of the main characteristics of osteoarthritic joints is cartilage degeneration. The cells in the temporomandibular joint (TMJ) cartilage are zonally arranged. The deep zone cells are differentiated from the superficial zone cells (SZCs). The purpose of the present study was to investigate whether degenerative shear stress (SS) stimulates the senescence programme in TMJ SZCs, and to determine which miRNA is involved in this process. MethodSZCs were isolated from the TMJ condyles of 3-week-old rats and treated with continuous passaging or SS. RNA sequencing was conducted to identify miRNA(s) that overlap with those involved in the replication senescence process and the SS-induced degeneration programme. Unilateral anterior crossbite (UAC), which is TMJ-OA inducible, was applied to 2-month-old and 12-month-old mice for 3 weeks. The effect of TMJ local injection of agomiR-708-5p was evaluated histologically. ResultsBoth replication and SS treatment induced SZC senescence. miR-708-5p was identified. Knocking down miR-708-5p in SS treated SZCs led to more severe senescence by alleviating the inhibitory impact of miR-708-5p on the TLR4/NF-κB pathway. miR-708-5p expression in mouse TMJ cartilage decreased with age. UAC induced more severe osteoarthritic cartilage lesions in 12-month-old mice than in 2-month-old mice. Injection of agomiR-708-5p suppressed UAC-induced osteoarthritic cartilage lesions. ConclusionsAge-related miR-708-5p deficiency is involved in the mechanically stimulated OA process. Intra-articular administration of agomiR-708-5p is a promising new strategy for OA treatment. Data availabilityThe small RNA and mRNA sequencing data included in this study are available in the NCBI Gene Expression Omnibus (GEO) database (accession numbers GSE236980, GSE236977, and GSE 236978).

The prevalence of bilateral and ipsilateral radiographic osteoarthritis is high in White, Asian and Native Hawaiian/Pacific Islanders presenting for unilateral knee or hip arthroplasty.

It is estimated that one-third of patients presenting with unilateral joint pain have contralateral osteoarthritis (OA) at first presentation. Most studies have primarily examined White patient cohorts. The purpose of this study was to determine the prevalence of contralateral joint OA for patients presenting for unilateral total knee (TKA), unicompartmental knee (UKA) or total hip arthroplasty (THA) among Asian, Native Hawaiian/Pacific Islander and White patients. Bilateral radiographic reports at initial presentation of 2,312 subjects who underwent unilateral arthroplasties (332 UKAs, 933 TKAs and 1,047 THAs) were reviewed. The presence of contralateral OA was recorded and compared by racial group and type of arthroplasty performed. Parametric statistical analyses were performed to determine differences between groups. Multivariable analyses were completed for each arthroplasty group to determine the influence on the presence of contralateral OA, presented as odds ratios and 95% confidence intervals. Contralateral joint OA was present in 86.7%, 90.4% and 70.4% of UKA, TKA and THA patients, respectively. Concurrent hip OA was present in 41.6% and 59.5% of UKA and TKA patients. No racial differences in the prevalence of contralateral knee OA were found for knee arthroplasty patients. White patients (74.6%) had a greater prevalence of contralateral hip OA compared to Asians (66.5%, p = 0.037) amongst THA recipients. Increased age and body mass index were significantly associated with the presence of contralateral knee OA. Increased age, being male and being White were significant contributors for the presence of contralateral hip OA. The prevalence of contralateral joint OA and concurrent hip OA is high in all three racial groups. Due to the extensive prevalence of contralateral and concurrent knee and hip OA, bilateral radiographic evaluation should be considered for all patients presenting with unilateral hip or knee pain due to OA.

Preoperative Adjacent Facet Joint Osteoarthritis Is Associated with the Incidence of Adjacent Segment Degeneration and Low Back Pain after Lumbar Interbody Fusion.

A retrospective cohort study. To analyze the association between preoperative adjacent facet joint osteoarthritis (FJOA) and outcomes of lumbar interbody fusion (LIF). Whether preoperative adjacent FJOA is associated with the incidence of radiological adjacent segment degeneration (RASD) and low back pain (LBP) relief after lumbar fusion remains unknown. The study included patients who underwent LIF. The demographic characteristics and radiographic and surgical data were collected and evaluated. The included patients were divided into control group and FJOA group based on the preoperative adjacent facet joint Pathria grade. Preoperative and last follow-up LBP Visual Analog Scale (VAS) score, leg pain (LP) VAS, Oswestry Disability Index (ODI) and RASD were evaluated and compared. The improvement rates in VAS and ODI were calculated and compared between the two groups. Logistic regression was used to analyze the risk factors of LBP relief and incidence of RASD. In total, 197 patients (control group, 86; FJOA group, 111) were included, and the median follow-up was 46 months. The VAS and ODI in both groups significantly improved after surgery. At the last follow-up, the FJOA group had higher VAS and lower VAS improvement rates of LBP than the control group (p<0.05). However, no significant difference in the LP VAS and ODI was found between the two groups. The incidence of RASD in the FJOA group was significantly higher than that in the control group (48.6% vs. 30.2%, p=0.034). Multivariate logistic regression analysis showed that preoperative adjacent FJOA was significantly associated with LBP relief (odds ratio [OR], 0.691; 95% confidence interval [CI], 0.498-0.958) and the postoperative incidence of RASD (OR, 1.406; 95% CI, 1.020-1.939). The preoperative FJOA in the adjacent segments was significantly associated with LBP following LIF. Patients with preoperative FJOA were more likely to have RASD following lumbar fusion surgery.

Effectiveness of Arthroscopic Debridement, Trapeziectomy, and Joint Replacement for Trapeziometacarpal Joint Osteoarthritis: A Meta-Analysis of Pre and Postoperative Pain Scores.

Trapeziometacarpal joint osteoarthritis (TMJO) affects up to 33% of postmenopausal women, leading to pain, reduced mobility, and grip strength, with initial treatments focusing on non-surgical options like injections, orthoses, and exercises before considering surgery. A major challenge in managing TMJO involves selecting the optimal surgical strategy that is customized to individual clinical conditions. This study aimed to compare the effectiveness of three common surgical interventions for TMJO in relieving pain, including arthroscopic debridement (AD), trapeziectomy (TRAP), and joint replacement (JR).PubMed, Cochrane, Embase, and MEDLINE databases were queried according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies that presented pain outcomes following intervention for TMJO. Pain scores were reported preoperatively and postoperatively using the visual analog scale (VAS). Inclusion criteria included studies published in Q1 and Q2 journals and those with a follow-up of > six months.The final selection comprised 18 studies with 763 patients treated with AD (n = 102, 13%), TRAP (n = 428, 56%), and JR (n = 233, 31%) between 2010 and 2023, with a mean follow-up period of 38 ± 28 months. The studies included a total of 24 groups, five of which received AD, 13 of which received TRAP, and six of which received JR. The mean preoperative VAS was 6.7 ± 1.7, and the mean postoperative VAS was 1.7 ± 1.3 for all groups (P < 0.001). The meta-analysis demonstrated a mean preoperative pain score of 5.8 (95% CI, 4.1-7.5) for AD, 6.6 (95% CI, 5.7-7.5) for TRAP, and 7.8 (95% CI, 7.0-8.7) for JR. Postoperatively, there was a mean pain score of 2.2 (95% CI, 0.1-4.2) for AD, 1.4 (95% CI, 1.1-1.7) for TRAP, and 0.9 (95% CI, 0.6-1.2) for JR.This study showed that, if appropriately indicated, joint preservation with AD may be as effective as TRAP and JR for reducing pain associated with TMJO in the short term. However, the rate of conversion or revision should be assessed in future studies.

Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages.

Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1β-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages.

Comparative study of 1H-NMR metabolomic profile of canine synovial fluid in patients affected by four progressive stages of spontaneous osteoarthritis

The study aimed to assess the metabolomic profile of the synovial fluid (SF) of dogs affected by spontaneous osteoarthritis (OA) and compare any differences based on disease progression. Sixty client-owned dogs affected by spontaneous OA underwent clinical, radiographic, and cytologic evaluations to confirm the diagnosis. The affected joints were divided into four study groups based on the Kallgreen–Lawrence classification: OA1 (mild), OA2 (moderate), OA3 (severe), and OA4 (extremely severe/deforming). The osteoarthritic joint’s SF was subjected to cytologic examination and 1H-NMR analysis. The metabolomic profiles of the study groups’ SF samples were statistically compared using one-way ANOVA. Sixty osteoarthritic joints (45 stifles, 10 shoulders and 5 elbows) were included in the study. Fourteen, 28, and 18 joints were included in the OA1, OA2, and OA3 groups, respectively (0 joints in the OA4 group). Metabolomic analysis identified 48 metabolites, five of which were significantly different between study groups: Mannose and betaine were elevated in the OA1 group compared with the OA2 group, and the 2-hydroxyisobutyrate concentration decreased with OA progression; in contrast, isoleucine was less concentrated in mild vs. moderate OA, and lactate increased in severe OA. This study identified different 1H-NMR metabolomic profiles of canine SF in patients with progressive degrees of spontaneous OA, suggesting 1H-NMR metabolomic analysis as a potential alternative method for monitoring OA progression. In addition, the results suggest the therapeutic potentials of the metabolomic pathways that involve mannose, betaine, 2-hydroxyisobutyrate, isoleucine, and lactate.

Metabolomic profiles of cartilage and bone reflect tissue type, radiography-confirmed osteoarthritis, and spatial location within the joint

Osteoarthritis is the most common chronic joint disease, characterized by the abnormal remodeling of joint tissues including articular cartilage and subchondral bone. However, there are currently no therapeutic drug targets to slow the progression of disease because disease pathogenesis is largely unknown. Thus, the goals of this study were to identify metabolic differences between articular cartilage and subchondral bone, compare the metabolic shifts in osteoarthritic grade III and IV tissues, and spatially map metabolic shifts across regions of osteoarthritic hip joints. Articular cartilage and subchondral bone from 9 human femoral heads were obtained after total joint arthroplasty, homogenized and metabolites were extracted for liquid chromatography-mass spectrometry analysis. Metabolomic profiling revealed that distinct metabolic endotypes exist between osteoarthritic tissues, late-stage grades, and regions of the diseased joint. The pathways that contributed the most to these differences between tissues were associated with lipid and amino acid metabolism. Differences between grades were associated with nucleotide, lipid, and sugar metabolism. Specific metabolic pathways such as glycosaminoglycan degradation and amino acid metabolism, were spatially constrained to more superior regions of the femoral head. These results suggest that radiography-confirmed grades III and IV osteoarthritis are associated with distinct global metabolic and that metabolic shifts are not uniform across the joint. The results of this study enhance our understanding of osteoarthritis pathogenesis and may lead to potential drug targets to slow, halt, or reverse tissue damage in late stages of osteoarthritis.

A comprehensive patient-specific prediction model for temporomandibular joint osteoarthritis progression

Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. The complexity of TMJ OA has hindered the development of prognostic tools, posing a significant challenge in timely, patient-specific management. Addressing this gap, our research employs a comprehensive, multidimensional approach to advance TMJ OA prognostication. We conducted a prospective study with 106 subjects, 74 of whom were followed up after 2 to 3 y of conservative treatment. Central to our methodology is the development of an innovative, open-source predictive modeling framework, the Ensemble via Hierarchical Predictions through Nested cross-validation tool (EHPN). This framework synergistically integrates 18 feature selection, statistical, and machine learning methods to yield an accuracy of 0.87, with an area under the ROC curve of 0.72 and an F1 score of 0.82. Our study, beyond technical advancements, emphasizes the global impact of TMJ OA, recognizing its unique demographic occurrence. We highlight key factors influencing TMJ OA progression. Using SHAP analysis, we identified personalized prognostic predictors: lower values of headache, lower back pain, restless sleep, condyle high gray level-GL-run emphasis, articular fossa GL nonuniformity, and long-run low GL emphasis; and higher values of superior joint space, mouth opening, saliva Vascular-endothelium-growth-factor, Matrix-metalloproteinase-7, serum Epithelial-neutrophil-activating-peptide, and age indicate recovery likelihood. Our multidimensional and multimodal EHPN tool enhances clinicians' decision-making, offering a transformative translational infrastructure. The EHPN model stands as a significant contribution to precision medicine, offering a paradigm shift in the management of temporomandibular disorders and potentially influencing broader applications in personalized healthcare.