Synthesis of fibronectin in normal and osteoarthritic articular cartilage

The content and the biosynthesis of fibronectin was examined in disease-free articular cartilage and in articular cartilage from osteoarthritic canine joints. Fibronectin content was increased in extracts of cartilage from osteoarthritic joints. Incubation of cartilage in vitro with [³H]phenylalanine and subsequent isolation of [³H]fibronectin from a gelatin affinity column and characterization by SDS-polyacrylamide gel electrophoresis and by immunoprecipitation indicated that disease-free and osteoarthritic cartilage explants synthesized fibronectin. About 50% of the [³H]fibronectin was recovered in the incubation medium. The osteoarthritic cartilage synthesized and accumulated up to 5-fold more [³H]fibronectin than disease-free cartilage.     

Aging in the musculoskeletal system of rhesus monkeys: I. Passive joint excursion

In order to describe ontogenetic change in the musculoskeletal system of rhesus monkeys, 126 Macaca mulatta from Cayo Santiago, ranging in age from 7 months to 21 years, were examined under anesthesia. Passive joint excursions were measured at the wrist, elbow, shoulder, hip, and knee. Mean ranges of excursion at these joints differed significantly between age groups and by sex. The potential for most movements appeared to decrease approximately 25 degrees over the first two decades of the macaque life span, and males generally showed less potential for movement than females in all age groups. These results are similar to those obtained for humans and are consistent with patterns of positional behavior, trauma, and osteoarthritis observed in this rhesus monkey population. Thus, to fully describe the locomotor strategy of rhesus monkeys, age- and sex-related variation in locomotor anatomy and functional capacity must be considered.     

Changes in osteoarthritis associated with the development of a maritime economy among southern California Indians

The severity of osteoarthritis was studied in human skeletal remains from archaeological sites in the Santa Barbara Channel area of southern California. These remains were analyzed to better understand changes in activity patterns associated with the economic shift from hunting and gathering to intensive fishing and craft specialization that occurred in this area. The joints of 967 burials from seven archaeological sites occupied between 3500 B.C. and the time of European contact were scored for osteoarthritis. These data show that the rate at which people developed osteoarthritis increased through time. This suggests that the adaptive shift toward more intensive exploitation of the marine environment resulted in an increase in the time people spent in strenuous physical activity. The increase in osteoarthritis affected males to a greater extent than females. One interpretation of this is that the work load of men increased with the economic importance of fishing.     

Osteoarthritis, calcium pyrophosphate deposition disease, and osseous infection in Old World primates.

Uncertainties as to the nature and implications of osteoarthritis and calcium pyrophosphate deposition disease (CPPD) in primates were subject to critical review through examination of 153 prosimians and 1,250 Old World non-prosimian primates. Osteoarthritis, calcium pyrophosphate deposition disease, and infectious arthritis/osteomyelitis were relatively rare phenomena, affecting only 1.7% and 2.5%, respectively, of free-ranging prosimians and other Old World non-prosimian primates. Frequency of infection in Indri and Presbytis appears to reflect a unique susceptibility or exposure. Papio may have a unique predisposition to CPPD. The dichotomy (frequency and joint distribution) between free-ranging and artificially restrained animals suggests caution in interpretation of osteoarthritis or CPPD in non-free-ranging animals.     

长非编码RNA SNAI3-AS1调控人软骨细胞C28/I2增殖能力及退变的机制研究

摘要 目的：为了探究长非编码RNA SNAI3-AS1（LncRNA SNAI3-AS1,即SNAI3-AS1）在骨性关节炎（osteoarthritis,OA）进展中的作用与机制。方法：通过全转录组测序筛选出在OA中差异表达的lncRNA SNAI3-AS1,并通过实时荧光定量PCR（qRT-PCR）检测SNAI3-AS1在软骨细胞退变模型中的表达情况。在软骨细胞C28/I2中分别转染SNAI3-AS1特异性siRNA或真核过表达质粒,分别敲低或过表达SNAI3-AS1,通过MTT、平板克隆形成和EdU掺入实验检测细胞增殖活力,Western Blot检测炎症和细胞外基质蛋白的表达情况。通过生物信息学网站预测SNAI3-AS1相互作用的miRNA和下游靶基因,并通过双荧光素酶报告基因和RIP实验进行验证。结果：相较于正常软骨细胞, SNAI3-AS1的表达水平在OA中显著下调。敲低正常软骨细胞中SNAI3-AS1的表达后,软骨细胞的增殖能力减弱并促进了软骨细胞的退变,而在OA模型的软骨细胞中过表达SNAI3-AS1后,软骨细胞的增殖活力加强并抑制了软骨细胞的退变。在机制上,SNAI3-AS1可充当竞争性内源性RNA（ceRNA）,经海绵吸附miR-2278间接上调PRELP,发挥促进软骨细胞增殖和抑制其退变的作用。结论：LncRNA SNAI3-AS1通过LncRNA SNAI3-AS1/ miR-2278/PRELP轴参与骨性关节炎的发生发展过程。     

3.0 T磁共振T2×mapping成像技术定量评估膝关节骨性关节炎的临床价值及与WOMAC评分的相关性分析

摘要 目的：研究3.0 T磁共振T2×mapping成像技术定量评估膝关节骨性关节炎（OA）的临床价值及与西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分的相关性。方法：将我院于2017年4月～2019年12月期间收治的膝关节OA患者80例纳入研究。根据K-L分级标准将膝关节OA患者分成轻度组（K-L分级为Ⅰ～Ⅱ级）32例,重度组（K-L分级为Ⅲ～Ⅴ级）48例。另取同期于我院进行体检的健康者30例作为对照组。所有受试者均接受3.0 T磁共振T2×mapping扫描,比较各组膝关节不同部位软骨T2值、WOMAC评分以及血清炎症因子水平,以Pearson相关性分析膝关节OA患者膝关节不同部位软骨T2值和WOMAC评分的关系。结果：重度组膝关节不同部位软骨T2值均高于轻度组以及对照组,且轻度组膝关节不同部位软骨T2值均高于对照组（均P＜0.05）。重度组各项WOMAC评分及总分均高于轻度组以及对照组,且轻度组各项WOMAC评分及总分均高于对照组（均P＜0.05）。经Pearson相关性分析发现：膝关节OA患者膝关节不同部位软骨T2值和各项WOMAC评分及总分均呈正相关（均P＜0.05）。重度组血清白介素-1β（IL-1β）、白介素-18（IL-18）、肿瘤坏死因子α（TNF-α）均高于轻度组以及对照组,且轻度组血清IL-1β、IL-18、TNF-α均高于对照组（均P＜0.05）。结论：3.0 T磁共振T2×mapping成像技术定量评估膝关节OA的临床价值较高,且患者膝关节不同部位软骨T2值与WOMAC评分密切相关。     

Investigation of the Molecular Nature of Low-molecular-mass Cobalt(II) Ions in Isolated Osteoarthritic Knee-joint Synovial Fluid

High field ¹H NMR spectroscopy demonstrated that addition of Co(II) ions to osteoarthritic knee-joint synovial fluid (SF) resulted in its complexation by a range of biomolecules, the relative efficacies of these complexants/chelators being citrate ? histidine ～ threonine?glycine ～ glutamate ～ glutamine ～ phenylalanine ～ tyrosine > formate > lactate?alanine > valine > acetate > pyruvate > creatinine, this order reflecting the ability of these ligands to compete for the available Co(II) in terms of (1) thermodynamic equilibrium constants for the formation of their complexes and (2) their SF concentrations. Since many of these SF Co(II) complexants (e.g. histidinate) serve as powerful ^?OH scavengers, the results acquired indicate that any of this radical generated from the Co(II) source in such complexes via Fenton or pseudo-Fenton reaction systems will be “site-specifically” scavenged. The significance of these observations with regard to cobalt toxicity and the in vivo corrosion of cobalt-containing metal alloy joint prostheses (e.g. CoCr alloys) is discussed.     

A method to induce Interleukin-1 Receptor Antagonist Protein from autologous whole blood

ObjectiveCurrent orthopedic therapies, aimed solely at symptomatic control, are unable to restore the cytokine imbalance that produces the hallmark clinical profile of osteoarthritis. While a myriad of chemical factors in the cytokine network stimulate local joint inflammation and pain, Interleukin 1 (IL-1) is widely recognized as a key offender and a potential therapeutic target. The purpose of this article is to describe a novel, on-site, point of service process (Arthrokinex™) to induce Interleukin 1 Receptor Antagonist Protein (IL-1-Ra or IRAP) from whole blood aimed at inhibiting the destructive intra-articular effects of IL-1.Methods53 patient charts were included in this retrospective chart review study. Venous blood from the selected participants had been harvested and centrifuged to isolate Platelet Rich Plasma and Platelet Poor Plasma. These layers were extracted and incubated for 30 min in a specialized syringe containing medical grade concentrator beads. After centrifuge filtration, the supernatant containing IL-1-Ra was extracted. Anti-inflammatory (IL-1-Ra, IL-10) and pro-inflammatory (TNF α, IL-1 β) cytokines of baseline whole blood were compared to the conditioned serum following quantification using ELISA.ResultsOn average, a 32-fold increase (baseline, 550 pg/mL; post conditioning 17,537 pg/mL) in IL-1-Ra concentration was observed after the brief interaction of blood with the concentrator bead surface. IL-1-Ra, if present in concentrations that are 10–100 times higher than IL-1β, will block the interaction of IL-1β with cell surface receptors. At these increased concentrations, Arthrokinex™ induced IL-1-Ra joint injections produce an IL-1-Ra to IL-1β ratio of 999:1. Post conditioning levels of IL-1β and TNF α were not clinically significant.ConclusionThe Arthrokinex™ blood conditioning process has the ability to rapidly induce IL-1-Ra without increasing the pro-inflammatory cytokine profile.     

橙皮素抑制NF-κB通路调控软骨细胞炎性退变的实验研究

目的:炎症因子所介导的慢性炎症瀑布反应是引起关节软骨退变的的主要原因。橙皮素具有抗炎、抗氧化应激等作用,研究橙皮素对关节软骨细胞炎症因子表达及相关信号通路的影响可以加深对关节软骨退变的认识,进而为其预防、治疗提供新的参考依据。研究橙皮素对人关节软骨细胞退变的影响,并从炎症角度来探讨其具体的分子机制。方法:体外分离培养人关节软骨细胞,首先采用CCK-8方法检测橙皮素对人关节软骨细胞增殖的抑制作用;运用RT-PCR和western blot研究橙皮素对于脂多糖(LPS)诱发的关节软骨细胞炎症反应和分解代谢的影响,运用Western blot研究橙皮素对于LPS所诱导的NF-κB信号通路的激活的影响。结果:当橙皮素的浓度低于10μM时,对于人关节软骨细胞的生长没有明显的抑制作用;real-time PCR和western blot结果显示,在LPS刺激下,关节软骨细胞中IL-6, TNF-α, MMP9, MMP13的基因表达水平明显升高,而橙皮素可以明显抑制炎症反应的激活;Western blot结果显示在LPS的刺激下,NF-κB信号通路显著激活,IKBα降解,随后P65磷酸化。而在橙皮素预处理组中,IKBα降解减少,P65磷酸化减少,NF-κB信号通路的激活受到了明显的抑制。以上结果均有统计学差异(P0.05)。结论:橙皮素可通过NF-κB信号通路影响人关节软骨细胞炎症反应和分解代谢相关基因的表达,进而降低关节软骨细胞内外的慢性炎症反应,进而延缓老年性关节软骨退变。     

Regional and disease-related differences in properties of the equine temporomandibular joint disc

Temporomandibular joint (TMJ) disorders affect up to 12% of the human population, and naturally occurring TMJ diseases are increasingly recognized in animals. The TMJ disc plays a major role in TMJ disorders in people, but little is known about its role in TMJ pathology in animals. This study characterizes differences in properties of equine TMJ discs associated with age, disc region, and presence of TMJ osteoarthritis (OA). Discs were dissected from both TMJ’s of sixteen horses euthanized for reasons unrelated to this study. Each joint was grossly evaluated and scored as normal, mild OA, or severe OA. Samples from the rostral, caudal, lateral, central, and medial regions of the disc were subject to compressive testing, quantitative biochemistry, and histology. Samples from the lateral, central, and medial region were tested for tensile properties in the rostrocaudal and mediolateral directions. We found that the equine TMJ disc is highly anisotropic, and its glycosaminoglycan (GAG) content and compressive stiffness vary between disc regions. The disc also exhibits increasing GAG content and compressive stiffness with increasing age. While equine TMJ disc properties are generally similar to other herbivores, greater compressive stiffness throughout the disc and greater GAG content in its rostral region suggest that mechanical demands on the TMJ disc differ between horses and other species. Importantly, a region-specific decrease in compressive stiffness was observed associated with joint disease and corresponded to cartilage erosions in the underlying condylar surface.