Normal Joint Research Articles

Variations in the Position of Mandibular Foramen in Temporomandibular Ankylosis Patients.

To evaluate the variation in the position of the mandibular foramen and mandibular canal in patients with and without temporomandibular joint ankylosis. 100 temporomandibular joints were evaluated of which 50 joints were ankylosed joints (Group A) and the rest 50 were normal joints (Group B) without ankylosis. These groups were further divided into those with growing potential (less than 18years) and those without growing potential (above 18years). The position of the mandibular foramen was measured from its center to the glenoid fossa, sigmoid notch, coronoid notch, gonion and posterior border on CBCT scans. The position of the mandibular canal was measured from the outer aspect of the canal to the lower border of the mandible, buccal and lingual cortical plates and the alveolus in the region of the 1st, 2nd and 3rd molars. The mean distance of the foramen from the base of the skull in Group A was 19.01mm while the same for Group B was 31.26mm. The mandibular foramen was found to be closer to the occlusal plane (5.43mm) in Group A as compared to the mean distance of 6.21mm reported in Group B. There was no significant difference in the position of the foramen from the posterior border, gonion and sigmoid notch between the groups. The mental foramen wasseen more commonly posterior to the 2nd premolar and closer to the first molar region in Group A while in Group B it was seen anterior or near the 2nd premolar. In Group A, the mean distance of the canal to the buccal cortical plate in the 1st and 2nd molar regions was 3.65mm and 5.76mm, respectively, while in Group B it was 6.09mm and 6.59mm. The canal was further away from the lower border in ankylosis cases (8.79mm) than the control group (7.41mm). On comparing the unaffected side in unilateral cases with the normal mandible, the canal and the foramen location were similar to that of a normal mandible with the values in the lower range that is usually seen in normal mandibles. Ankylosis of the mandible is a debilitating condition especially when it develops in an individual prior completion of growth as it can affect the mandibular anatomy. Understanding the variations that accompany a deranged mandible can assist the surgeon in planning of surgical procedures in a manner that limits the possible complications resulting from surgery.

Comparative morphology of the cruciate ligaments: A radiological study.

The anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) are important structures to maintain knee stability. The present study aimed to further enrich understandings of the morphology of the cruciate ligaments and explore the relationship between the diameter of ACL and PCL. This study collected valid MRI samples of 50 male and 50 female normal right knee joints and measured the diameter of each point of the ACL and PCL through the 3D Slicer. The diameter of the ACL in the sagittal MRI of the normal right knee joint was significantly different from the diameter of each point of the PCL. The average diameter of each point of the ACL was larger than the diameter of the corresponding point of the PCL. Males and females had statistical differences in their PCL origin point, PCL midpoint, ACL origin point, ACL midpoint, and ACL insertion point diameters under sagittal MRI examination. The average diameter of males was greater than the average diameter of females at the above corresponding sites. In sagittal MRI scans of the normal right knee joint, we observed that only the origin point of the PCL exhibited a moderate correlation with the midpoint and insertion point of the ACL in terms of their respective diameters. The correlation between diameters of normal ACL and PCL in knee joint MRI was moderate and may help clinicians determine appropriate graft for cruciate ligament reconstruction surgery quickly for severe cruciate ligament injuries.

Finite element analysis of anterior cruciate ligament reconstruction techniques: A comparison of the mechanical properties of all-inside fixation and traditional fixation.

The main purpose of this study was to explore the mechanical properties of the anterior cruciate ligament and its attachments following reconstruction with the all-inside technique after anterior cruciate ligament injury. Knee joint computed tomography data were collected from healthy volunteers, and knee joint models were created using Mimics software. A normal knee joint model, an all-inside reconstructed anterior cruciate ligament model, and a traditional reconstructed anterior cruciate ligament model were established. A tensile force of 134N and a bending moment of 5N/m were applied at the anterior aspect of the proximal tibia in these three models. The knee joint was subjected to external rotation, internal rotation, varus, valgus, flexion, and extension under this bending moment. The magnitude and distribution of stress on the ligament or graft and the magnitude and distribution of stress on the graft attachments were observed under different loading conditions. Under different external forces, the maximum stress on the ligament in the normal model fluctuated from 1.949 to 18.302MPa, with an uncertain distribution of maximum stress. The maximum stress on the graft in the all-inside reconstructed anterior cruciate ligament model fluctuated from 0.705 to 3.465MPa and was mainly distributed at the junction of the graft and the tibial footprint. In the traditional reconstructed anterior cruciate ligament model, the maximum stress on the graft fluctuated from 5.012 to 59.269MPa and was primarily distributed at the junction of the interference screw and the graft. The concentration of stress on the loop and plate in the all-inside reconstructed anterior cruciate ligament model fluctuated from 70.461 to 346.363MPa, with maximum stress distributed at the junction of the loop and the tibial surface. The maximum stress on the interference screw in the traditional reconstructed anterior cruciate ligament model fluctuated from 10.184 to 92.298MPa, with maximum stress primarily distributed at the end of the interference screw. Under different external forces, the graft used in all-inside anterior cruciate ligament reconstruction is subjected to fewer external forces than that used in traditional anterior cruciate ligament reconstruction, which may indicate a relatively stable mechanical environment. The strength of the loop and plate can theoretically tolerate daily knee joint movements of patients without injury.

Cluster Analysis of Normal Ankle Joint X-ray Morphology of Han Adults in Shaanxi Province, China

Cluster Analysis of Normal Ankle Joint X-ray Morphology of Han Adults in Shaanxi Province, China

Shoulder shake-up: Unveiling the unusual case of acute melioidosis

BackgroundMelioidosis is one of the emerging infections in India and is often neglected due to lack of awareness among clinicians. The diseases usually present as multifocal or focal abscesses with bacteremia, yet the isolated septic monoarthritic complicated with septic venous thrombosis is a rare presentation. CaseThis case report describes a 48-year-old male business executive with diabetes and alcoholism who developed septic arthritis caused by Burkholderia pseudomallei and no clear history of exposure to the organism. The patient initially experienced fever, chills, fatigue, reduced urine output, and signs of early sepsis. Despite initial improvement with fluid therapy and antibiotics, the patient's fever persisted. Meticulous clinical examination revealed signs of inflammation and movement restriction in the left shoulder which letter on became obvious and the main complaints of patient. Blood cultures confirmed the presence of B. pseudomallei. Imaging showed septic arthritis, osteomyelitis, lymphadenitis, and venous thrombosis in the left shoulder. Surgical debridement was performed, and the tissue cultures showed the growth of the same pathogen. This led to significant clinical improvement and with prolonged course of antibiotics, complete resolution of symptoms and normal joint function was achieved. ConclusionThis case report serves to highlight the rare and atypical presentation of Melioidosis and the importance of suspecting this infection in nonendemic regions underscoring the probable impact of climate change. Early diagnosis, effective source control measures and prolonged antibiotic therapy, emerges as pivotal factors contributing to favorable outcomes in such cases.

Severe calcinosis circumscripta in multiple foot pads in a 5- month old pomeranian puppy secondary to renal disease – a case report

A 5-month old Pomeranian puppy with lameness in all four limbs, polydipsia, polyuria, vomiting, and melena observed approximately for one month was presented to the Veterinary Teaching Hospital, University of Peradeniya. The metacarpal and metatarsal foot pads of all four limbs were swollen with chalky white, mottling. The differential diagnoses for the foot pad lesions were fungal granuloma, calcinosis circumscripta, and neoplasia. The fine needle aspirates obtained from the foot pad lesions were chalky white, gritty, and microscopically consistent with mineral deposits. Plain radiographs of the metacarpals revealed deposition of radiopaque material in metacarpal and digital foot pads with normal bones and joints. Based on the gross lesions, radiography, and fine needle aspiration cytology, a tentative diagnosis of calcinosis circumscripta of foot pads was made. Haematology and serum chemistry revealed microcytic hypochromic anaemia and mild azotaemia. Abdominal ultrasonography revealed small right and left kidneys with increased overall echogenicity and poor corticomedullary differentiation. The historical, clinical, radiographic, and ultrasonographic findings were suggestive of calcinosis circumscripta in multiple foot pads with concurrent renal disease. The very young age of the dog was highly suggestive of renal dysplasia as the cause of concurrent renal disease. Despite the supportive and symptomatic treatments, the puppy died five days after the presentation. This appears to be the first report of calcinosis circumscripta of foot pads with evidence of renal disease diagnosed in a dog less than one year old.

Anthropometric evaluation of side, sex and age by radiological examination of the normal ankle joint among adult Egyptian population

PurposeSex and age estimation is important, particularly when information about the deceased is unavailable. There are limited radiological studies investigating side, sex and age differences in normal ankle morphometric parameters. The authors’ goal was to evaluate different ankle joint morphometric measurements and document variations among Egyptians.Design/methodology/approachA prospective study was conducted throughout 23 months on 203 (100 males and 103 females) adult Egyptians, aged between 20-69 years old, who were referred for a plain x-ray of bilateral normal ankle joints.FindingsAnkle parameters showed no statistical difference between both sides, except for tarsal width (TaW) which was significantly higher on right than left side (26.92 ± 2.66 vs 26.18 ± 2.65 mm). Males showed significantly higher morphometric values except for anteroposterior gap (APG) and talus height (TaH) which were significantly higher in females (2.29 ± 0.80 vs 1.80 ± 0.61 mm and 13.01 ± 1.68 vs 11.87 ± 1.91 mm, respectively). There was significant increase in tibial arc length, APG, distance of level of MTiTh from anterior limit of mortise, distance of level of MTiTh from vertex of mortise, sagittal distance between tibial and talar vertices and sagittal radius of trochlea tali arc in old age group compared to young one. A significant decrease in tibial width, malleolar width, TaW and TaH was noted in old age group compared to young one.Originality/valueAnkle joints of both sides are mostly symmetrical; however, there are significant differences in most morphometric values due to sex and age factors. These findings may be essential during side, sex and age determination.

Pathological progress and remission strategies of osteoarthritic lesions caused by long-term joint immobilization

ObjectiveWhile joint immobilization is a useful repair method for intra-articular ligament injury and periarticular fracture, prolonged joint immobilization can cause multiple complications. A better understanding how joint immobilization and remobilization impact joint function and homeostasis will help clinicians develop novel strategies to reduce complications.DesignWe first determined the effects of long-term immobilization on joint pain and osteophyte formation in patients after an extraarticular fracture or ligament injury. We then developed a mouse model of joint immobilization and harvested the knee joint samples at 2, 4, and 8 weeks. We further determined the effects of remobilization on recovery of the osteoarthritis (OA) lesions induced by immobilization in mice.ResultsWe found that the long-term (6 weeks) joint immobilization caused significant joint pain and osteophytes in patients. In mice, 2-week immobilization already induced moderate sensory innervation and increased pain sensitivity and infiltration in synovium without inducing marked osteophyte formation and cartilage loss. Long-term immobilization (4 and 8 weeks) induced more severe sensory innervation and inflammatory infiltration in synovium, massive osteophyte formation on both sides of the femoral condyle, and the edge of the tibial plateau and significant loss of the articular cartilage in mice. Remobilization, which ameliorates normal joint load and activity, restored to certain extent some of the OA lesions and joint function in mice.ConclusionsJoint immobilization caused multiple OA-like lesions in both mice and humans. Joint immobilization induced progressive sensory innervation, synovitis, osteophyte formation, and cartilage loss in mice, which can be partially ameliorated by remobilization.

CP-25 inhibits the hyperactivation of rheumatic synoviocytes by suppressing the switch in Gαs-Gαi coupling to the β2-adrenergic receptor

In essence, the β2 adrenergic receptor (β2AR) plays an antiproliferative role by increasing the intracellular cyclic 3’,5’-adenosine monophosphate (cAMP) concentration through Gαs coupling, but interestingly, β2AR antagonists are able to effectively inhibit fibroblast-like synoviocytes (FLSs) proliferation, thus ameliorating experimental RA, indicating that the β2AR signalling pathway is impaired in RA FLSs via unknown mechanisms. The local epinephrine (Epi) level was found to be much higher in inflammatory joints than in normal joints, and high-level stimulation with Epi or isoproterenol (ISO) directly promoted FLSs proliferation and migration due to impaired β2AR signalling and cAMP production. By applying inhibitor of receptor internalization, and small interfering RNA (siRNA) of Gαs and Gαi, and by using fluorescence resonance energy transfer and coimmunoprecipitation assays, a switch in Gαs-Gαi coupling to β2AR was observed in inflammatory FLSs as well as in FLSs with chronic ISO stimulation. This Gαi coupling was then revealed to be initiated by G protein coupled receptor kinase 2 (GRK2) but not β-arrestin2 or protein kinase A-mediated phosphorylation of β2AR. Inhibiting the activity of GRK2 with the novel GRK2 inhibitor paeoniflorin-6′-O-benzene sulfonate (CP-25), a derivative of paeoniflorin, or the accepted GRK2 inhibitor paroxetine effectively reversed the switch in Gαs-Gαi coupling to β2AR during inflammation and restored the intracellular cAMP level in ISO-stimulated FLSs. As expected, CP-25 significantly inhibited the hyperplasia of FLSs in a collagen-induced arthritis (CIA) model (CIA FLSs) and normal FLSs stimulated with ISO and finally ameliorated CIA in rats. Together, our findings revealed the pathological changes in β2AR signalling in CIA FLSs, determined the underlying mechanisms and identified the pharmacological target of the GRK2 inhibitor CP-25 in treating CIA.7HWufKwpH5ZfY_hx8fyY6aVideo

General joint hypermobility in temporomandibular joint disease; clinical characteristics, biomarkers, and surgical aspects

ObjectivesThis study aimed at identifying biomarkers in the temporomandibular joint (TMJ) synovial tissue analysing 28 extra cellular matrix proteins in TMJ diseased patients, classified with either general joint hypermobility (GJH) or normal joint mobility (NJM), and to compile clinical and protein characterisation to reveal potential surgical predictive factors. Study designA prospective observational cohort study including 97 consecutive patients scheduled for TMJ surgery was performed. Joint mobility and several other predefined clinical variables were recorded. Synovial tissue was harvested during surgery followed by examination using multi-analytic profiling. A multivariate quantile regression model was used for analysis purposes. ResultsThe GJH/NJM ratio was 2:5. The GJH cohort were younger (P = 0.001) and more likely to be women (P = 0.026) compared to the NJM cohort. None of the protein concentrations could be correlated to joint mobility in the multivariate regression model, but often to the variable TMJ diagnosis. The surgical outcome after the six-month follow-up were equal between GJH and NJM patients. ConclusionsGJH was more common in the study cohort compared to general population frequencies, but GJH was not a negative factor for surgical outcome. Young age and female gender correlated to GJH. No TMJ biomarkers were GJH specific, and the results suggested that TMJ diagnosis more strongly correlated to the protein profile compared to GJH and the other investigated variables.

Increased Circulating Levels of YKL-40 Protein in Children and Adolescents with Hemophilia: Correlation with the Degree of Hemophilic Arthropathy

Introduction: Hemophilia A and B are rare X-linked inherited bleeding disorders caused by complete or partial deficiency of coagulation factors VIII and IX, respectively. Recurrent joint bleeding (hemarthrosis) is the most frequent clinical manifestation of severe hemophilia. Unless appropriately managed, even subclinical hemarthrosis can lead to hemophilic arthropathy, that severely affects the quality of life of patients. Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a 40-kDa heparin-human cartilage glycoprotein without enzymatic activity, that is encoded by the CHI3L1 gene in humans and its name derives from the one letter code for the three terminal amino acids - tyrosine (Y), lysine (K) and leucine (L). YKL-40 is secreted in vitro and in vivo in the arthritic joint by various cell types, such as activated macrophages, chondrocytes, synoviocytes and neutrophils. Actually, it is a major protein that has been identified in the chondrocytes from arthritic knee joints.In fact, synovial as well as serum YKL-40 levels are found increased in joint diseases like rheumatoid arthritis and osteoarthritis, indicating its potential role as a biomarker of inflammation and tissue remodeling or degradation, whereas it is absent in normal joints. In our knowledge, there are not any reports linking YKL-40 expression with hemophilic arthropathy, thus we aimed to investigate if this protein could be implicated in hemophilic arthropathy severity, by measuring its circulating levels and correlate them with hemophilic arthropathy features and laboratory parameters in children and adolescents with hemophilia A and B. Patients and Methods: Eighty children and adolescents (median age:14 years, range 10-18 years) with severe (n= 60), moderate (n= 8) and mild (n= 12) hemophilia A or B (n= 7), on prophylaxis or on demand treatment (n= 12) were included in the study, while 35 apparently healthy male individuals matched for age served as controls. No signs of hemophilic arthropathy (NHAP), i.e. Hemophilia Joint Health Score 2.1 ≤ 2 and Hemophilia Early Detection Arthropathy with Ultrasound Score ≤ 1, were detected in 34/80 patients with median age of 13.5 years. In 37/80 patients with median age of 14.25 years arthropathy (HAP) was confirmed, while 18/80 patients with median age of 15.75 years presented with acute bleeding (AB)-hemarthrosis or muscle bleed- at the time of the laboratory evaluation. In patients and controls YKL-40 concentrations were determined by means of an immunoenzymatic technique. Results: We found that: a) Circulating YKL-40 levels in patients with hemophilia were significantly higher compared to controls, 21.9±2.3 ng/mL (95% Confidence Intervals of the mean (CI): 19.6;24.2 ng/mL) vs 17.0±2.5 ng/mL (CI: 14.5;19.4 ng/mL), respectively, p=0.003. b) Patients with arthropathy (HAP) tend to express higher circulating YKL-40 levels (25.5±2.0 ng/mL) than patients without arthropathy (NHAP)(20.1±1.8 ng/mL) and patients with acute bleeding (AB) (19.7±2.4 ng/mL), respectively, p-trend=0.06. Conclusions: To the best of our knowledge, this is the first study to evaluate the potential clinical significance of circulating YKL-40 levels in patients with hemophilia and demonstrated that it could reflect hemophilic arthropathy activity in clinical or even in subclinical level. As YKL-40 in synovial fluid is derived from cells in the inflamed/damaged synovium, such as chondrocytes, we postulate that it may be involved in the pathophysiology of the hemophilic arthropathy processes and reflect local disease activity. Further studies are essential on the role of YKL-40 in the evolution of hemophilic arthropathy, in order to fully elucidate its clinical significance and prognostic utility.

Ligamentous Knee Joint Instability: Association with Chronic Conditions of the Knee and Treatment with Prolotherapy

Ligamentous knee joint instability and other conditions associated with knee dysfunction are common musculoskeletal complaints that affect a large percentage of the global population. A healthy knee has normal joint mechanics and can maintain its stability as it responds to the forces placed upon it. Once undue forces, whether from injury, wear and tear, or overuse, cause the soft tissue structures of the knee to stretch beyond their normal range of motion, they can become lax, elongated, damaged, or torn, especially the ligaments. This condition, known as ligamentous knee instability, causes destructive joint forces to occur, which results in the development of other pathophysiologic conditions related to knee dysfunction, including osteoarthritis, patellar pain syndromes, tendinopathies, meniscus tears, and osteochondral defects. Traditional treatments address the consequences of joint instability, such as synovitis and joint swelling, but do not address the underlying ligament and/or disease that led to the joint instability. Prolotherapy promotes the repair of injured or degenerated tissues, such as ligaments, tendons, and menisci, by stimulating the physiological healing process of the joint. This process corrects the underlying joint instability, reduces associated pain, improves knee function, and has the potential to slow the degenerative process.

Recent advances in porous nanomaterials‐based drug delivery systems for osteoarthritis

AbstractOsteoarthritis (OA) is a common degenerative disease that develops over time, characterized mainly by inflammatory joints, cartilage deterioration, and ultimately loss of normal joint function. Some of the limitations that restrict the effectiveness of current OA treatment procedures include minimal penetration of medications into cartilage and lack of vascularity, leading to insufficient bioavailability and systemic toxicity. To increase the effectiveness of treatment, it is necessary to create novel non‐invasive OA treatment techniques. Porous nanomaterials (PNMs) show great promise as sustained drug delivery systems (DDSs) due to their functionality, variable porosity, and high loading capacity. In addition, they can provide targeted drug delivery, facilitate controlled release of drugs, and prolong drug circulation and retention time while reducing adverse reactions and improving drug solubility. First, the current treatment methods and challenges are summarized. Subsequently, recent advances in DDSs for OA treatment based on PNMs with various pore sizes and structures are presented. Lastly, the parameters that affect the performance of DDSs are discussed by giving some suggestions for their design. The purpose of this review is to provide new insights into PNM‐based DDS design and to inspire readers to adopt the smart design of intra‐articular DDSs in the future.

Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. The signaling lymphocytic activation molecule (SLAMF) family of receptors are expressed on various hematopoietic and non-hematopoietic cells and can regulate both immune cell activation and cytokine production. Altered expression of certain SLAMF receptors contributes to aberrant immune responses in RA. In RA, SLAMF1 is upregulated on T cells and may promote inflammation by participating in immune cell-mediated responses. SLAMF2 and SLAMF4 are involved in regulating monocyte tumor necrosis factor production and promoting inflammation. SLAMF7 activates multiple inflammatory pathways in macrophages to drive inflammatory gene expression. SLAMF8 inhibition can reduce inflammation in RA by blocking ERK/MMPs signaling. Of note, there are differences in SLAMF receptor (SFR) expression between normal and arthritic joint tissues, suggesting a role as potential diagnostic biomarkers. This review summarizes recent advances on the roles of SLAMF receptors 1, 2, 4, 7, and 8 in RA pathogenesis. However, further research is needed to elucidate the mechanisms of SLAMF regulation of immune cells in RA. Understanding interactions between SLAMF receptors and immune cells will help identify selective strategies for targeting SLAMF signaling without compromising normal immunity. Overall, the SLAMF gene family holds promise as a target for precision medicine in RA, but additional investigation of the underlying immunological mechanisms is needed. Targeting SLAMF receptors presents opportunities for new diagnostic and therapeutic approaches to dampen damaging immune-mediated inflammation in RA.

Normal joint range of motion in children with Down syndrome.

Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective of this study was to establish normative joint ROM values, using a standardized measurement approach, for upper and lower joints of healthy children of both genders with DS. This study evaluated joint ROM in healthy males and females with DS who had no previous musculoskeletal pathology. Younger males have more ROM than females at the same age and both genders lose ROM with age but continue to have increased ROM in the ankles compared to children without DS. This study establishes optimal estimates of joint ROM in children with DS, and this information should be helpful to clinicians when assessment requires evaluation of joint ROM to know if evaluation falls within the normal ROM. This reference should be helpful to track joint disease progression over time or as part of a musculoskeletal screen for abnormal joint ROM in children with DS.

Numerical simulations of the effect of lateral malleolus fracture malunion on ankle biomechanics: Different offset directions and offsets

IntroductionAnkle fractures account for approximately 10 % of all fractures. Approximately 5–68 % of patients with ankle fractures may suffer from malunion. Besides, suboptimal reduction of fracture fragments can affect the biomechanics of the ankle joint, ultimately leading to damage to the ankle joint. However, there are certain controversies over the conclusion of previous cadaveric studies. MethodsIn this study, a three-dimensional model of the ankle joint was established based on CT image data. In addition, the effects of backward offset (1–2 mm) and outward offset (0.5–1 mm) of the fracture fragment on the contact area, contact pressure, and ligament force of the ankle joint were investigated via the finite element method. Moreover, lateral malleolus fracture malunion in five ankle positions (neutral, 10° dorsiflexion, 10° plantarflexion, 20° dorsiflexion, and 20° plantarflexion) was investigated. ResultsThis model predicted an overall increased contact area in the ankle joint in patients with lateral malleolus fracture malunion compared with the normal ankle joint. The results demonstrated that the outward offset had a more significant effect than the backward one. The larger the dorsiflexion-plantarflexion angle, the more pronounced the effect of malunion. Further, an outward offset can cause the fibula to lose its function. ConclusionPost-traumatic osteoarthritis occurs under the action of unaccustomed cartilage forces due to altered tibial talar joint contact patterns, rather than increased contact pressure reported in previous studies. Malunion leads to an increase or decrease in force on the affected ligament, while the cause of malunion can be envisioned based on a decrease in the force on the ligaments.

Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation.

15-Lipoxygenase-1 (15-LOX-1) catalyzes the biosynthesis of many anti-inflammatory and immunomodulatory lipid mediators and was reported to have protective properties in several inflammatory conditions, including osteoarthritis (OA). This study was designed to evaluate the expression of 15-LOX-1 in cartilage from normal donors and patients with OA, and to determine whether it is regulated by DNA methylation. Cartilage samples were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee joint replacement surgery. The expression of 15-LOX-1 was evaluated using real-time polymerase chain reaction (PCR). The role of DNA methylation in 15-LOX-1 expression was assessed using the DNA methyltransferase inhibitor 5-Aza-2'-desoxycytidine (5-Aza-dC). The effect of CpG methylation on 15-LOX-1 promoter activity was evaluated using a CpG-free luciferase vector. The DNA methylation status of the 15-LOX-1 promoter was determined by pyrosequencing. Expression of 15-LOX-1 was upregulated in OA compared to normal cartilage. Treatment with 5-Aza-dC increased 15-LOX-1 mRNA levels in chondrocytes, and in vitro methylation decreased 15-LOX-1 promoter activity. There was no difference in the methylation status of the 15-LOX-1 gene promoter between normal and OA cartilage. The expression level of 15-LOX-1 was elevated in OA cartilage, which may be part of a repair process. The upregulation of 15-LOX-1 in OA cartilage was not associated with the methylation status of its promoter, suggesting that other mechanisms are involved in its upregulation.

A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment.

This study investigates repeated low-dose lipopolysaccharide (LPS) injections in equine joints as a model for recurrent joint inflammation and its impact on animal welfare. Joint inflammation was induced in eight horses by injecting 0.25 ng of LPS three times at two-week intervals. Welfare scores and clinical parameters were recorded at baseline and over 168 h post-injection. Serial synoviocentesis was performed for the analysis of a panel of synovial fluid biomarkers of inflammation and cartilage turnover. Clinical parameters and a final synoviocentesis were also performed eight weeks after the last sampling point to assess the recovery of normal joint homeostasis. Statistical methods were used to compare the magnitude of response to each of the 3 LPS inductions and to compare the baseline and final measurements. Each LPS injection produced consistent clinical and biomarker responses, with minimal changes in welfare scores. General matrix metalloproteinase (MMP) activity and joint circumference showed greater response to the second LPS induction, but response to the third was comparable to the first. Gylcosaminoglycans (GAG) levels showed a significantly decreased response with each induction, while collagen-cleavage neoepitope of type II collagen (C2C) and carboxypropetide of type II collagen epitope (CPII) showed quicker responses to the second and third inductions. All parameters were comparable to baseline values at the final timepoint. In conclusion, a consistent, reliable intra-articular inflammatory response can be achieved with repeated injections of 0.25 ng LPS, with minimal impact on animal welfare, suggesting potential as a refined translational model of recurrent joint inflammation.

Which inflammatory marker might be the best indicator for sacroiliitis?

AbstractThis study aimed to investigate the potential of inflammatory markers, including platelet‐to‐lymphocyte ratio (PLR), neutrophil‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and C‐reactive protein‐to‐lymphocyte ratio (CLR), in identifying sacroiliitis. Present retrospective study was conducted at the Abant Izzet Baysal University Hospital, including patients diagnosed with sacroiliitis between August 2020 and March 2023. Control subjects with normal sacroiliac joints were also included. Sacroiliitis patients were further categorized into active and chronic sacroiliitis groups. Demographic data and laboratory characteristics, such as erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and various blood parameters, were recorded. Inflammatory markers were calculated, including PLR, NLR, LMR, and CLR. Statistical analyses were performed to compare the study groups and evaluate the diagnostic performance of these markers. A total of 226 subjects, including 132 sacroiliitis patients and 94 control subjects, were included in the study. Serum CRP levels were significantly higher in sacroiliitis patients compared to the control group. NLR, PLR, and CLR values were elevated in sacroiliitis patients, while LMR was decreased. There were significant correlations between these markers and established inflammatory markers. Receiver operating characteristic (ROC) analysis demonstrated moderate diagnostic performance for NLR, PLR, LMR and CLR in detecting sacroiliitis. Inflammatory markers, specifically NLR, PLR, LMR and CLR, showed significant differences between sacroiliitis patients and the control group. In addition PLR is useful in distinguishing active and chronic sacroiliitis. These markers, in conjunction with established inflammatory markers, may serve as supportive diagnostic tools for sacroiliitis.

Patellar Dislocation: Workup and Decision-Making.

Acute patellar dislocation (PD) is usually a problem of adolescents and young adults. In most cases, it is a sports-related injury. It is the result of an indirect force on the knee joint, which leads to valgus and external rotation of the tibia relative to the femur. PD is unlikely to occur on a knee with normal patellofemoral joint (PFJ) anatomy. Acute PD consists of an acute injury of the ligamentous medial patellar stabilizers in the background of factors predisposing to patellar instability. These factors are classified into three groups. The first group refers to the integrity of the ligamentous medial patellar restraints, particularly, the medial patellofemoral ligament (MPFL). The second group refers to an abnormal PFJ anatomy, which renders the patella inherently unstable inside the trochlea. The third group refers to the overall axial and torsional profile of the lower limb and to systemic factors, such as ligament laxity and neuromuscular coordination of movement. PD at a younger age is associated with an increased number and severity of patellar instability predisposing factors and lower stress to dislocate the patella. Acute primary PD is usually treated conservatively, while surgical treatment is reserved for recurrent PD. The aim of treatment is to restore the stability and function of the PFJ and to reduce the risk of patellar redislocation. Surgical procedures to treat patellar instability are classified into non-anatomic and anatomic procedures. Non-anatomic procedures are extensor mechanism realignment techniques that aim to center the patella into the trochlear groove. Anatomic procedures aim to restore the PFJ anatomy (ruptured ligaments, osteochondral fractures), which has been severed after the first incident of PD. Anatomic procedures, especially MPFL reconstruction, are more effective in preventing recurrent PD, compared with non-anatomic techniques. Theoretically, all factors that affect PFJ stability should be evaluated and, if possible, addressed. This is practically impossible. Considering that the MPFL ruptures in almost all PDs, MPFL reconstruction is the primary procedure, which is currently selected by most surgeons as a first-line treatment for patients with recurrent PD. Restoration of the axial and torsional alignment of the lower limbs is also increasingly implemented by surgeons. Non-anatomic surgical techniques, such as tibial-tuberosity osteotomy, are used as an adjunct to anatomic procedures. In the presence of multiple PFJ instability factors, acute MPFL reconstruction may be the treatment of choice for acute primary PD as well. Skeletal immaturity of the patient precludes osseous procedures to avoid premature physis closure and subsequent limb deformity. Unfortunately, restoration of the patient's previous activity level or participation in more strenuous sports is questionable and not easy to predict. In the case of competitive athletes, PD may prevent participation in elite levels of sports.