Subchondral Sclerosis Research Articles

Остеоартроз в различных экологических регионах. Сообщение 2. Связь с состоянием питьевой воды

Целью работы стала оценка клинико-патогенетических связей остеоартроза (ОА) с качественным составом питьевой воды в зонах проживания больных. Материал и методы. Под наблюдением находились 133 больных первичным ОA в возрасте 58,90 ± 0,83 года. Оценивали в 33 городских и сельских регионах уровни жесткости и минерализации питьевой воды, концентрации в ней хлоридов, сульфатов, фосфатов и нитратов, содержание токсичных микроэлементов (Ba, Li, Ni, Pb). Результаты. Низкое качество питьевой воды в регионах проживания людей способствует развитию ОА в более молодом возрасте, что в последующем определяет интегральную тяжесть артикулярного синдрома, характер костно-деструктивных изменений в суставах (развитие остеопороза, остеоузур, хондромных тел), формирование манифестного реактивного синовита (концентрации хлоридов и нитратов), темпы прогрессирования заболевания, появление внутрисуставных отложений кальцинатов, остеофитоза и эпифизарного остеопороза (степень минерализации и жесткости воды). Тяжесть ОА и темпы прогрессирования костно-деструктивных изменений со стороны суставов зависят от уровня микроэлементов, которые определяют распространенность суставного синдрома, развитие узелков Гебердена и/или Бушара, спондилопатии, степень реактивного синовита, остеопороза, субхондрального склероза, лигаментоза, интраартикулярных хондромных тел и тел Гоффа, а высокое содержание Pb является фактором риска неблагоприятного течения заболевания. Выводы: выявлены определенные клинико-патогенетические связи ОА с качественным составом питьевой воды в регионах проживания больных.

Реологические свойства сыворотки крови при метаболическом синдроме у больных остеоартрозом

Интегральные реологические свойства сыворотки крови больных остеоартрозом зависят от наличия всех составляющих метаболического синдрома (в первую очередь от параметров инсулинемии, тяжести инсулинорезистентности, индекса массы тела, урикемии, липидемии, типа гиперлипидемии, характера артериальной гипертензии и периферического сосудистого сопротивления), а в патогенезе таких признаков, как остеофитоз, остеокистоз, остеоузурация, остеопороз, субхондральный склероз, поражение менисков, развитие кист Бейкера и энтезопатий, участвуют показатели адсорбционно-гликемического интегрального коэффициента, гликемического коэффициента межфазной активности, модуля вязкоэластичности, статического поверхностного натяжения и фазового угла тензиограмм.

Содержание меди и цинка в организме больных ревматоидным и псориатическим артритами

При ревматоидном и псориатическом артритах развивается Cu-Zn-микроэлементоз, который участвует в патогенетических построениях заболеваний. Концентрации в крови этих микроэлементов оказывают воздействие на распространенность, стадию и тяжесть патологического процесса, влияя на развитие внутрисуставных кальцификатов, выраженность дигитального артериита, патологии периферической нервной системы, нарушений диастолической функции левого желудочка сердца, а по уровням купремии и цинкемии можно оценивать характер течения патологического процесса. Повышенное содержание Cu в крови наблюдается у каждого второго больного псориазом, причем с возрастом у них уменьшается содержание Zn, которое определяется распространенностью суставного синдрома, а показатели содержания Cu в волосах зависят от характера суставного синдрома, выраженности сужения суставных щелей, субхондрального склероза и остеокистоза.

ANALYSIS OF RISK FACTORS AFFECTING LUMBAL FACET JOINT OSTEOARTHRITIS IN MRI SCAN

Background: Osteoarthritis is a long-term, chronic disease that is usually marked by cartilage degeneration in the joints, which in turn induces bone friction. One of the subtype of this disease is facet joint osteoarthritis or in short, FJOA. In Indonesia, FJOA has not been commonly documented. The most common method for FJOA inspection is X-Ray modality. The usage of other radiology imaging, such as CT-Scan or MRI, are also used to evaluate erosion, osteophyte creation, subchondral sclerosis, and joint constriction. Nevertheless, the most ideal FJOA inspection method is still an ongoing debate due to strengths and weaknesses of each methods. CT scans are more widely used than MRIs and are typically less expensive. MRIs, however, are thought to be superior in regards to the detail of the image. Objective: To understand the effect of age, sex, and spinal level towards FJOA on MRI scanning. Method: This research used cross-sectional approach. Sample taken in this research were all radiology results from patients that fulfills inclusion criteria and had gone through MRI inspection in Jatinegara Premier Hospital. Age, sex, disk degeneration degree, and spinal level are the main focus for this study since those are the most common risk factor for FJOA. Results: 46.8% of FJOA were found in male patients while the other 53.2% were found in females. L4-5 and Grade 1 FJOA had the highest incidence found, with the amount of 29% and 48.4% respectively. There was no correlation between sex and FJOA degree based on Asymp. Sig of 0.255. There was also no correlation between age and FJOA degree based on Asymp. Sig of 0.702. However, there was a correlation between spinal level and disk degeneration degree with FJOA degree due to Asymp. Sig <0.05. Conclusion: There was no significant relationship between age and sex to lumbar facet joint osteoarthritis and there was a significant relationship between spinal level and disk degeneration degree with lumbar facet joint osteoarthritis.

Do Knee-Straining Activities Influence the Subchondral Bone Microarchitecture and Accelerate Knee Osteoarthritis Progression?

Knee overload was detrimental to knee osteoarthritis subjects. We aim to analyze the association between the subchondral bone microarchitecture sclerosis and typical knee-straining activities. The frequency of experiencing squatting, kneeling, lifting, and climbing of 481 knee osteoarthritis subjects was investigated. Subchondral bone microarchitecture (bone volume fraction, trabecular thickness, trabecular separation, and trabecular number) was measured by the fast imaging with steady-state free precession magnetic resonance imaging applying trabecular sequencing, at baseline and 12-mo follow-up. Logistic regression was conducted to investigate the relationship between microarchitecture change and each knee-straining activity, adjusted by age, sex, weight, and Kellgren-Lawrence grade. All data were from the Osteoarthritis Initiative. Long kneeling was associated with increased bone volume fraction (adjusted odds ratio = 1.16, confidence interval = 1.01-1.33) and trabecular number (adjusted odds ratio = 1.16, confidence interval = 1.02-1.33). Long squatting was associated with a lower risk of increased trabecular separation (adjusted odds ratio = 0.84, confidence interval = 0.71-0.98) and a higher risk of increased trabecular thickness (adjusted odds ratio = 1.29, confidence interval = 1.06-1.55). Long squatting also increased the medial compartment joint width narrowing (-0.21 in squatting group vs -0.03 in no squatting group, P < 0.05). Knee osteoarthritis patients should avoid long squatting and kneeling, and subchondral bone microarchitecture possesses excellent potential as a monitoring indicator in subjects who kneel or squat for long.

CT is a feasible imaging technique for detecting lesions in horses with elbow lameness: A study of 139 elbows in 99 horses

AbstractComputed tomography (CT)is increasingly available in veterinary referral practices; however, published studies describing CT lesions of the equine elbow are currently lacking. In this single‐center, retrospective, observational study, horses undergoing elbow CT at Equitom between July 2015 and October 2018 were reviewed. Subchondral bone sclerosis; resorption of the radius, ulna, and humerus; osteophyte; and enthesophyte lesions were graded. One hundred thirty‐nine elbows of 99 horses (16 with elbow pain and 123 control elbows) were included (median age, 9 years). Osseous cyst‐like lesions (n = 13), only seen in the proximomedial radius and medial humerus, were the most common cause of lameness in horses with elbow pain (n = 16), with significantly higher grades of bone resorption (including osseous cyst‐like lesions) in this group. One elbow had an avulsion fracture of the lateral epicondyle, two others showed signs of osteoarthritis. Significantly higher grades of sclerosis in the proximomedial radius were seen in horses with elbow pain; however, mild to moderate subchondral bone sclerosis was seen in all horses at the medial aspect of the joint. Osteochondral fragmentation lesions of the weight‐bearing surface of the medial radius (2/16 vs 1/123; P = .0025) and intra‐articular gas (4/16 vs 2/123; P &lt; .0001) were significantly more common in horses with elbow pain compared to control horses. Mild linear resorptive subchondral bone lesions were often not clinically relevant (32/123 vs 5/16 in medial humerus; 19/123 vs 2/16 in medial radius). In conclusion, elbow CT is a feasible method for detecting clinically relevant lesions in adult Warmblood horses with elbow pain.

Baicalein Alleviates Osteoarthritis Progression in Mice by Protecting Subchondral Bone and Suppressing Chondrocyte Apoptosis Based on Network Pharmacology

As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.

Increased expression of osteopontin in subchondral bone promotes bone turnover and remodeling, and accelerates the progression of OA in a mouse model.

Osteopontin (OPN) has been proved to be closely related to the pathogenesis of osteoarthritis (OA), but the role of OPN in the pathogenesis of OA has not been fully clarified. Current studies on OPN in OA mostly focus on articular cartilage, synovial membrane and articular fluid, while ignoring its role in OA subchondral bone turnover and remodeling. In this study, we used a destabilization OA mouse model to investigate the role of OPN in OA subchondral bone changes. Our results indicate that increased expression of OPN accelerates the turnover and remodeling of OA subchondral bone, promotes the formation of h-type vessels in subchondral bone, and mediates articular cartilage degeneration induced by subchondral bone metabolism. In addition, our results confirmed that inhibition of PI3K/AKT signaling pathway inhibits OPN-mediated OA subchondral bone remodeling and cartilage degeneration. This study revealed the role and mechanism of OPN in OA subchondral bone, which is of great significance for exploring specific biological indicators for early diagnosis of OA and monitoring disease progression, as well as for developing drugs to regulate the metabolism and turnover of subchondral bone and alleviate the subchondral bone sclerosis of OA.

Frequency and anatomic distribution of magnetic resonance imaging lesions in the sacroiliac joints of spondyloarthritis and non-spondyloarthritis patients.

Background:Lesions detected by magnetic resonance imaging (MRI) of the sacroiliac joints are critical to the diagnosis of non-radiographic axial spondyloarthritis. However, inflammatory and structural lesions may be encountered in other conditions.Objectives:The objective of this study was to evaluate and compare the frequency and localization of inflammatory and structural lesions on MRIs of the sacroiliac joint of spondyloarthritis (SpA) and non-spondyloarthritis (non-SpA) patients.Design:This is a retrospective study including 200 patients, each having undergone an MRI of the sacroiliac joints.Methods:Two experienced readers evaluated the whole set of images to detect erosions, subchondral sclerosis, fatty lesions, bone marrow edema (BME) and ankylosis according to the definitions established by the ASAS MRI working group. We divided sacroiliac joints into five segments: upper, antero-middle, intermediate-middle, postero-middle and lower.Results:A total of 96 subjects with SpA (mean age 37.4 ± 11.8 years) and 104 without SpA (mean age 39.9 ± 11.6 years) were included. Of the 96 SpA patients, 65% had inflammatory buttock pain compared with 25% in the non-SpA group. BME was seen in 65% of SpA patients, mainly in the intermediate-middle segment, and in 20% of non-SpA patients, predominantly in the antero-middle segment. Subchondral sclerosis occurred in 44% of non-SpA patients, mostly in the antero-middle segment, and in 36% of SpA patients. Fatty lesions were present in 34% of SpA and in 21% of non-SpA patients. Erosions were seen in 25% of non-SpA and in 60% of SpA patients. BME and structural lesions were minimally observed in the postero-middle segment in non-SpA patients.Conclusion:Inflammatory and structural lesions were observed in all segments of the joint in SpA, mainly in the middle segments, while lesions predominantly affected the antero-middle segment in non-SpA, and were uncommon in the postero-middle segment.

Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice.

Osteoarthritis (OA) is the most common degenerative joint disease affecting the older populations globally. Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c), a lipid kinase catalyzing the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), is involved in various cellular processes, such as focal adhesion (FA) formation, cell migration, and cellular signal transduction. However, whether Pip5k1c plays a role in the pathogenesis of OA remains unclear. Here we show that inducible deletion of Pip5k1c in aggrecan-expressing chondrocytes (cKO) causes multiple spontaneous OA-like lesions, including cartilage degradation, surface fissures, subchondral sclerosis, meniscus deformation, synovial hyperplasia, and osteophyte formation in aged (15-month-old) mice, but not in adult (7-month-old) mice. Pip5k1c loss promotes extracellular matrix (ECM) degradation, chondrocyte hypertrophy and apoptosis, and inhibits chondrocyte proliferation in the articular cartilage of aged mice. Pip5k1c loss dramatically downregulates the expressions of several key FA proteins, including activated integrin β1, talin, and vinculin, and thus impairs the chondrocyte adhesion and spreading on ECM. Collectively, these findings suggest that Pip5k1c expression in chondrocytes plays a critical role in maintaining articular cartilage homeostasis and protecting against age-related OA.

LATERAL TIBIOFEMORAL 3‐D JOINT SPACE WIDTH AND BONE PARAMETERS IN COMBINATION ARE SIGNIFICANTLY RELATED TO PROGRESSION OF LATERAL AND MEDIAL COMPARTMENT JOINT SPACE NARROWING: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

An important development in osteoarthritis imaging has been the ability to assess joint space width (JSW) from weight bearing CT (WBCT). The value of combining JSW with subchondral bone parameters in disease assessment is less well understood, particularly with respect to disease phenotype. To investigate associations of worsening medial and lateral tibiofemoral compartment structural disease over 2 years with a multivariate combination of baseline 3-D JSW and bony parameters from WBCT. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study along with same-visit and 2-year follow-up medial and lateral OARSI joint space narrowing (JSN) grade. After semi-automatic segmentation of 663 available knees, joint space mapping delivered 3-D JSW maps. Cortical bone mapping was performed to measure trabecular attenuation (TA), endocortical thickness (ET), and subchondral thickness (ST) at the femoral (f) and tibial (t) surfaces. A template was registered to each individual joint surface, a 3-D statistical shape model created, and all 7 spatially co-located parameters transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of JSW plus each bone parameter in turn on the experimental variables of 2-year medial and lateral OARSI JSN worsening. One knee per participant was used, selecting the side with greater JSN worsening, randomly if equal. 10 knees did not have radiographic grading, so the analysis used single knees from 394 individuals. 218 were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28.5 ± 5.0 kg/m 2 . SPM results (figs 1-4 below) revealed significant parameter ROIs in the lateral tibiofemoral compartment that were associated with worsening of medial and lateral OARSI JSN grade at 2 years. Baseline lateral compartment JSW was significantly wider by up to ∼1 mm (unmasked lateral compartment blue zone in fig. 1) in combination with lower baseline tTA by up to ∼25 attenuation units (AU) (unmasked lateral compartment red zone in fig. 2) for each increment in future medial JSN over 2 years. The reverse was demonstrated for future lateral JSN with narrower baseline lateral JSW by up to ∼1 mm (unmasked lateral compartment red zone in fig. 3) in combination with higher baseline tTA by up to ∼25 AU (unmasked lateral compartment blue zone in fig. 4) for each grade of future lateral JSN over 2 years. Baseline JSW was significantly narrower at the lateral margin of the lateral compartment by up to ∼1 mm in combination with thicker tST and fST by up to ∼0.2 mm for each grade of future lateral JSN (not shown). Baseline medial 3-D JSW did not relate to any substantial significant future narrowing for any JSW-bone parameter combination for future medial or lateral JSN. ET results (with JSW) were very similar to those for ST at both sides of the joint. 3-D JSW analysed in combination with bone parameters at the lateral (but not medial) tibiofemoral compartment are significantly related to future medial and lateral OARSI JSN grade. Lower lateral compartment tTA (with higher JSW) is related to future medial JSN and may be an effect of trabecular remodelling from reduced lateral loading, while greater thickness of subchondral and endocortical bone in the lateral compartment (alongside lower JSW) can be explained by subchondral sclerosis. These results suggest the lateral compartment warrants closer attention for following both medial and lateral compartmental progression. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com .

3-D DISTRIBUTION OF BONE PARAMETERS ACROSS THE DISTAL FEMUR FROM WEIGHT BEARING CT FOLLOWS PATTERNS ACCORDING TO JOINT SPACE NARROWING PHENOTYPE: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

Weight bearing CT (WBCT) technology has been increasingly used in imaging of knee osteoarthritis in recent years because of its ability to assess the weight bearing joint space. However, relatively little is known regarding the extent to which this cone beam technology can provide useful information on peri-articular bone beyond the subchondral regions. To explore relationships between WBCT-derived 3-D cortical bone thickness and trabecular bone attenuation at the distal femur with concurrent joint space narrowing phenotypes. WBCT imaging was obtained ancillary to the Multicenter Osteoarthritis Study at the 144-month visit. After semi-automatic segmentation, femoral cortical thickness (fCT) and trabecular attenuation (fTA) maps were created for each of 663 available distal femurs using cortical bone mapping. A template was registered to each individual distal femur and a 3-D statistical shape model created, followed by transfer of fCT and fTA distribution maps onto the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of fCT and fTA in turn on the experimental variables of concurrent radiographic medial and lateral OARSI joint space narrowing (JSN) grade. One knee from each participant was selected for inclusion, taking the side with worse compartmental baseline JSN grade or randomly if equal. 16 knees were excluded due to unachievable registration, with a final study set of a single knee from 386 individuals. 219 were female, mean ± SD age was 63.6 ± 9.6 yrs, mass 82.3 ± 17.7 kg, height 169 ± 9 cm, and BMI 28.5 ± 5.0 kg/m 2 . SPM significance ROIs according to baseline medial (left, figs 1 & 2) and lateral (right, figs 3 & 4) JSN phenotypes are shown for fCT (top row, figs 1 & 3) and fTA (bottom row, figs 2 & 4). SPM revealed significantly greater fCT by up to ∼0.1mm and fTA by up to ∼40 attenuation units (AU) for each increment in baseline JSN grade along the outer margin of the respective compartments (unmasked blue zones in each figure). Significantly greater fCT by up to ∼0.1mm for each increment in medial JSN grade also spread across the anterior aspect of the medial femoral condyle suggesting a wider regional relationship. 3-D distribution of fCT and fTA follow distinct patterns according to OARSI JSN phenotype, relating to recognised distributions of marginal osteophytosis and subchondral sclerosis. These results indicate that cone beam WBCT can quantify cardinal bony structural features of osteoarthritis and that their distribution is related to specific osteoarthritis OARSI JSN phenotypes. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com

Sinensetin attenuates IL-1β-induced cartilage damage and ameliorates osteoarthritis by regulating SERPINA3.

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, synovial hyperplasia and osteophyte formation as the main pathological manifestations. Age, mechanical stress and inflammation are the main factors that induce joint degeneration in the pathogenesis of OA. Sinensetin (SIN) is a natural flavonoid with anti-inflammatory and antioxidant properties. This study aims to investigate the effect of SIN on OA. We have investigated the anti-inflammatory and chondroprotective effects of SIN on IL-1β-induced human OA chondrocytes and a rat OA model. In vitro, human chondrocytes were induced by 5 ng mL-1 IL-1β and treated with different concentrations of SIN. The results suggest that SIN can inhibit IL-1β-induced overproduction of pro-inflammatory mediators in human OA chondrocytes, including COX2, iNOS, TNF-α and IL-6, and also reduce the production of MMP13 and MMP9, thus protecting the degradation of the extracellular matrix. In addition, SIN can inhibit the activation of NF-κB by regulating the expression of SERPINA3. In an in vivo experiment, rats were randomly divided into 3 groups, namely the sham operation group, OA model group and SIN group, and were given normal saline or 20 mg kg-1 SIN, respectively. The knee cartilage tissue was removed 6 weeks after surgery for analysis and detection, and our studies have shown that SIN can effectively delay the progression of OA in rats and protect cartilage. In conclusion, our study shows that SIN has good application potential in the treatment of OA.

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

BackgroundUncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components. Gingko biloba is a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown.MethodsIn our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), from Gingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored.ResultsIn interleukin-1β-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB’s chondroprotection with the AMPK-specific inhibitor Compound C abrogated it.ConclusionsThese results demonstrated that BB extracted from Gingko biloba regulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as a de novo therapeutic insight for OA.Graphical Schematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herb Gingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.

Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model

BackgroundAnimal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging. MethodsKnees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as control from 6 to 33 weeks of age were evaluated by histological grading systems for joint tissues (cartilage, meniscus, synovium, and subchondral bone), and µCT analysis. Gene expression patterns in articular cartilage were analyzed by real-time PCR. Immunohistochemistry was performed for OA-related factors, senescence markers, and apoptosis.ResultsStarting at 14 weeks of age, SAMP8 exhibited mild OA-like changes such as proteoglycan loss and cartilage fibrillation. From 18 to 33 weeks of age, SAMP8 progressed to partial or full-thickness defects with exposure of subchondral bone on the medial tibia and exhibited synovitis. Histological scoring indicated significantly more severe OA in SAMP8 compared with SAMR1 from 14 weeks [median (interquartile range): SAMR1: 0.89 (0.56–1.81) vs SAMP8: 1.78 (1.35–4.62)] to 33 weeks of age [SAMR1: 1.67 (1.61–1.04) vs SAMP8: 13.03 (12.26–13.57)]. Subchondral bone sclerosis in the medial tibia, bone mineral density (BMD) loss of femoral metaphysis, and meniscus degeneration occurred much earlier than the onset of cartilage degeneration in SAMP8 at 14 weeks of age.ConclusionsSAMP8 are a spontaneous OA model that is useful for investigating the pathogenesis of primary OA and evaluating therapeutic interventions.

The effect of natural mineral bicarbonate sodium-calcium water «Tib-1» on the antioxidant status of rats with adjuvant rheumatoid arthritis

Study of the effect of natural mineral water « Tib-1» on the lipid peroxidation system in an experiment with a model adjuvant-induced RA in rats. The object of the study were Wistar rats, divided into three groups: negative control (solvents), positive control (model of adjuvant-induced RA by subcutaneous injection of complete Freund's adjuvant) and experimental (correction of RA with mineral water « Tib-1», diluted in a ratio of 1:3 during the first 2 weeks from the moment the model was formed in the ad libitum mode). On the 3rd and 7th weeks in the blood of the animals were determined: the total number of leukocytes, the content of hydroperoxides according to Gavrilov, the level of malondialdehyde (MDA), catalase activity. Pathological changes in the hip and knee joints were recorded using radiography. The inflammatory process in the positive control group by the 3rd week was characterized by an increase in the number of leukocytes by 66% (p<0.01) and was accompanied by an increase in MDA by 60% (p<0.001). By the 7th week, despite a relative increase in catalase activity (16%), the MDA level continued to be elevated compared to the negative control by 67% (p<0.001). Against the background of exposure to mineral water, inflammation decreased (the number of leukocytes in the "model/experiment" groups turned out to be reduced by 41%; p<0.01) and an increase in compensatory-adaptive reactions in the form of catalase activation was noted (by 8%; p<0.01), which was accompanied by a persistent (weeks 3 and 7) decrease in MDA output (by 20%; p<0.01). Using the method of radiation diagnostics, positive changes in the articular apparatus of experimental animals were revealed, consisting in the relief of signs of subchondral sclerosis of the bone heads, which were noted for animals of the model group. The use of natural mineral water «Tib-1» helps to reduce the acute inflammatory response during the formation of adjuvant-induced RA in Wistar rats, initiates the normalization of the balance of pro- and antioxidant processes in the body, and minimizes the intensity of degenerative-inflammatory joint lesions.

The Impact of Trace Elements on Osteoarthritis.

Osteoarthritis (OA) is a progressive degenerative disease characterized by cartilage degradation, synovial inflammation, subchondral sclerosis and osteophyte formation. It has a multifactorial etiology with potential contributions from heredity, endocrine function, abnormal mechanical load and nutrition. Of particular considerations are trace element status. Several trace elements, such as boron and magnesium are essential for normal development of the bone and joint in human. While cadmium correlates with the severity of OA. The present review focuses on the roles of trace elements (boron, cadmium, copper, iron, magnesium, manganese, selenium, zinc) in OA and explores the mechanisms by which they act.

Intra-articular Injection of Lornoxicam and MicroRNA-140 Co-loaded Cationic Liposomes Enhanced the Therapeutic Treatment of Experimental Osteoarthritis.

Osteoarthritis is a chronic joint disease characterized by chronic inflammation, progressive destruction of articular cartilage, and subchondral bone sclerosis. When compared to individual treatment, the combined administration of genes and small-molecule drugs for osteoarthritis may not only provide superior inflammation control and pain relief, but may also repair cartilage damage. Here, cationic liposomes (CL) were used to deliver small hydrophobic drugs and microRNA into chondrocytes to treat osteoarthritis. Lornoxicam cationic liposomes (Lnxc-CL) were prepared by film dispersion, and loaded with microRNA-140 (miR-140) by electrostatic interaction to obtain cationic liposomes co-loaded with lornoxicam and miR-140 (Lnxc-CL/miR-140). The prepared Lnxc-CL/miR-140 had a particle size of 286.6 ± 7.3nm, polydispersity index (PDI) of 0.261 ± 0.029 and zeta potential of 26.5 ± 0.5mV and protected miR-140 from RNase degradation for 24h. Lnxc-CL/miR-140 was evaluated for its ability to regulate gene expression in chondrocytes in vitro and to provide in vivo therapeutic effects for knee osteoarthritis in rats. The results of in vitro uptake experiments and polymerase chain reaction (PCR) analysis showed that Lnxc-CL/miR-140 efficiently delivered miR-140 into chondrocytes and up-regulated the expression of miR-140 and COL2A1 mRNA. Pharmacodynamics studies demonstrated that Lnxc-CL/miR-140 effectively treated osteoarthritis by eliminating joint inflammation and repairing damaged cartilage cells, with superior therapeutic effects compared to Lnxc or miR-140 alone. Overall, the findings of this study support the co-delivery of Lnxc and miR-140 with cationic liposomes as a potential new therapeutic strategy for the treatment of osteoarthritis.

Developing a grading scale for the evaluation of degenerative changes in uncovertebral (Luschka) joints.

The study aimed to develop a grading scale for evaluating degenerative changes in uncovertebral joints (UVJs) found on computed tomography (CT) scans, and assess the intra- and inter-rater reliability of this scale. The study included 50 subjects (average age 55.12 ± 13.76 years) referred for CT examinations due to cervical complaints. Three researchers developed a reading protocol using a semiquantitative grading scale of UVJ degenerative changes. CTs were read and reread several times to refine the protocol. Subsequently, the reader read and reread 20 CTs (C3-C7 bilateral, altogether 200 UVJs) 2 weeks apart in order to assess the intra-rater reliability. The second reader, after the training, read the same 20 CTs (yet, C4-C6 bilateral, altogether 120 UVJs) in order to assess the inter-rater reliability. The additional 30 CTs were evaluated to analyze the prevalence and associations between the studied parameters. The final grading scale included joint space narrowing, osteophyte, subchondral sclerosis, subchondral cyst, hypertrophy, cortical erosion, and vacuum phenomenon. The intra-rater agreement ranged from very good in joint space narrowing (k= 0.757), osteophyte grade (k= 0.748), subchondral cyst (k= 0.716), hypertrophy (k= 0.728), vacuum phenomenon (k= 0.712) to good (k= 0.544) in subchondral sclerosis, and fair in cortical erosion (k= 0.36). For the overall UVJ degeneration grade, the intra-rater agreement was very good (k= 0.616) and the inter-rater reliability was good (k= 0.468). 77.6% of the evaluated UVJs exhibited some degenerative changes. Our grading scale is the first to evaluate UVJs presenting good-very good intra-rater and inter-rater reliability which can be utilized in further clinical studies and assess degenerative changes in UVJs.

The Emerging Role of Non-Coding RNAs in Osteoarthritis.

Osteoarthritis (OS) is the most frequent degenerative condition in the joints, disabling many adults. Several abnormalities in the articular cartilage, subchondral bone, synovial tissue, and meniscus have been detected in the course of OA. Destruction of articular cartilage, the formation of osteophytes, subchondral sclerosis, and hyperplasia of synovial tissue are hallmarks of OA. More recently, several investigations have underscored the regulatory roles of non-coding RNAs (ncRNAs) in OA development. Different classes of non-coding RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been reported to affect the development of OA. The expression level of these transcripts has also been used as diagnostic tools in OA. In the present article, we aimed at reporting the role of these transcripts in this process. We need to give a specific angle on the pathology to provide meaningful thoughts on it.