The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

三维超声对胎儿体表畸形的诊断价值

目的:探讨三维超声成像在胎儿体表畸形诊断的临床价值。方法:利用三维超声仪对在我院进行产前检查的妊娠20~41周的3241例孕妇、共3277个胎儿进行二维及三维超声检查,统计并比较超声诊断与随访结果。结果:140例各种发育异常胎儿,其中体表畸形胎儿34例,二维超声诊断正确者21例,9例体表畸形胎儿二维超声检查不能作出明确诊断;三维超声进一步检查诊断正确者共30例;二维及三维超声检查误诊1例胎儿足内翻,生后证实正常,漏诊1例耳廓缺失、2例多指畸形,生后随访证实。三维超声对胎儿体表畸形检出的敏感性、特异性及准确性分别为90.91%、99.97%、99.88%;二维超声对胎儿体表畸形检出的敏感性、特异性及准确性分别为63.64%、99.97%、99.60%。结论:三维超声能直观显示胎儿体表结构,三维超声检查诊断胎儿体表畸形的敏感性、特异性及准确性高,是二维超声检查的重要补充,与二维超声联合应用,可提高胎儿体表畸形的检出率。     

Membrane-seeded autologous chondrocytes: cell viability and characterization at surgery

The implantation of chondrocytes, seeded on matrices such as hyaluronic acid or collagen membranes, is a method that is being widely used for the treatment of chondral defects. The aim of the present study was to evaluate the distribution, viability and phenotype expression of the cells seeded on a collagen membrane just at the time of the implantation. Twelve patients who were suffering from articular cartilage lesions were treated by the MACI^® procedure. The residual part of each membrane was tested by colorimetric assay (MTT) and histochemical and ultrastructural analyses were carried out. In all of the samples a large number of viable cells, quite homogenously distributed, was detected. The cells expressed the markers of the differentiated hyaline chondrocytes. These data reassure in that the MACI procedure provides a suitable engineered tissue for cartilage repair, in line with the clinical evidences emerging in the literature.     

Investigation of melt agglomeration process with a hydrophobic binder in combination with sucrose stearate

The melt agglomeration process of lactose powder with hydrogenated cottonseed oil (HCO) as the hydrophobic meltable binder was investigated by studying the physicochemical properties of molten HCO modified by sucrose stearates S170, S770 and S1570. The size, size distribution, micromeritic and adhesion properties of agglomerates as well as surface tension, contact angle, viscosity and specific volume of molten HCO, with and without sucrose stearates, were examined. The viscosity, specific volume and surface tension of molten HCO were found to be modified to varying extents by sucrose stearates which are available in different HLB values and melt properties. The growth of melt agglomerates was promoted predominantly by an increase in viscosity, an increase in specific volume or a decrease in surface tension of the molten binding liquid. The agglomerate growth propensity was higher with an increase in inter-particulate binding strength, agglomerate surface wetness and extent of agglomerate consolidation which enhanced the liquid migration from agglomerate core to periphery leading to an increased surface plasticity for coalescence. The inclusion of high concentrations of completely meltable sucrose stearate S170 greatly induced the growth of agglomerates through increased specific volume and viscosity of the molten binding liquid. On the other hand, the inclusion of incompletely meltable sucrose stearates S770 and S1570 promoted the agglomeration mainly via the reduction in surface tension of the molten binding liquid with declining agglomerate growth propensity at high sucrose stearate concentrations. In addition to being an agglomeration modifier, sucrose stearate demonstrated anti-adherent property in melt agglomeration process. The properties of molten HCO and melt agglomerates were dependent on the type and concentration of sucrose stearate added.     

人工股骨头置换术治疗高龄非稳定性股骨转子间骨折

目的探讨高龄患者非稳定性股骨转子间骨折行人工股骨头置换术的临床疗效。方法本组74例，年龄75～89岁，平均80．3岁；骨折类型按Evans分类：ⅢA型31例，ⅢB型24例，Ⅳ型19例。其中3例为经内固定治疗失败病例，合并内科疾病者69例，在相关内科协同治疗后行双极骨水泥型人工股骨头置换术，术后早期进行康复锻炼。结果74例都顺利通过手术，住院期间无死亡病例；72例获得随访，随访时间3～16个月，平均9．2个月；无一例出现畸形，髋关节功能接近或恢复到受伤前水平，生活可自理；2例于出院后5个月、11个月死于其他疾病。结论人工股骨头置换术治疗高龄非稳定性股骨转子间骨折是一种效果确切的治疗方法，操作简单、创伤小、卧床时间短、并发症低、死亡率低，提高了高龄患者的生活质量。