Influence of TNF-α and biomechanical stress on matrix metalloproteinases and lysyl oxidases expressions in human knee synovial fibroblasts

Purpose

It was reported that not only ACL but also the synovium may be the major regulator of matrix metalloproteinases (MMPs) in synovial fluids after ACL injury. In order to further confirm whether synovium is capable of regulating the microenvironment in the process of ACL injury, the complicated microenvironment of joint cavity after ACL injury was mimicked and the combined effects of mechanical injury and inflammatory factor [tumour necrosis factor-α (TNF-α)] on expressions of lysyl oxidases (LOXs) and MMPs in synovial fibroblasts derived from normal human synovium were studied.

Methods

Human normal knee joint synovial fibroblasts were stimulated for 1–6 h with mechanical stretch and inflammatory factor (TNF-α). Total RNA was harvested, reverse transcribed and assessed by real-time polymerase chain reaction for the expression of LOXs and MMP-1, 2, 3 messenger RNAs. MMP-2 activity was assayed from the collected culture media samples using zymography.

Results

Compared to control group, our results showed that 6 % physiological stretch increased MMP-2 and LOXs (except LOXL-3), decreased MMP-1 and MMP-3; injurious stretch (12 %) decreased LOXs (except LOXL-2)and increased MMP-1, 2 and 3; the combination of injurious stretch and TNF-α decreased LOXs and increased MMP-1, 2 and 3 in synovial fibroblasts in a synergistical manner.

Conclusion

This study demonstrated that combination of mechanical injury and inflammatory factors up-regulated the expressions of MMPs and down-regulated the expressions of LOXs in synovial fibroblasts, eventually alter the balance of tissue healing. Thus, synovium may be involved in regulating the microenvironment of joint cavity. Based on the mechanism, early interventions to inhibit the production of MMPs or promote the production of LOXs in the synovial fibroblasts should be performed to facilitate the healing of tissue.     

Differential BMP-1 expression in injured anterior cruciate ligament and medial collateral ligament fibroblasts induced by TGF-β1

目的 观察在转化生长因子-β1(transforming growth factor betal,TGF-β1)作用下,损伤的前交叉韧带(anterior cruciate ligament,ACL)和内侧副韧带(medial collateral ligament,MCL)中骨形态发生蛋白-1(bone morphogenetic protein-1,BMP-1)基因的表达,找出TGF-31、BMP-1之间的关系,揭示机械损伤后ACL和MCL细胞中BMP-1的表达差异.方法 采用反转录PCR(RT-PCR)和实时荧光定量PCR方法检测1、5、50 ng/ml TGF-β1处理后2h受损的ACL和MCL细胞中BMP-1的表达以及5 ng/ml TGF-β1作用2、6、12、24h受损的ACL和MCL细胞中BMP-1的表达;Western blot检测5 ng/mlTGF-β1处理48 h后受损的ACL和MCL细胞中BMP-1的表达.结果 受损的ACL和MCL细胞中BMP-1的基因表达比正常状态下偏高,并随着TGF-β1浓度的增大而增高,在MCL中的增高程度比在ACL中高出近1倍(P＜0.05);与正常组相比,在5 ng/ml TGF-β1处理24h后,ACL细胞中BMP-1的表达在24h达到最高比例(约为6.1倍),而在MCL中12h达到最高比例(约为9.84倍,P＜0.05).5 ng/ml TGF-β1处理48 h后BMP-1蛋白也明显上调,与无TGF-β1处理的对照组相比,ACL细胞中BMP-1上调2.32倍,MCL细胞中BMP-1上调3.84倍(P＜0.05).结论 TGF-β1刺激BMP-1的变化可能直接影响到细胞外基质中活性赖氨酰氧化酶的表达,对损伤ACL和MCL的修复有极其重要的参考价值和临床意义.     

Postural stability in altered and unaltered sensory environments following fatiguing exercise of lower extremity joints

Investigations of postural recovery following controlled external perturbations have provided models for healthy and pathological balance behavior. Less work, however, has investigated postural responses related to internal perturbations of the balance system. In this study, lower extremity joint (knee, or ankle) and overall fatigue of the dominant leg provided the internal perturbations to the balance system. Postural sway was examined during unilateral dominant leg standing before and immediately following fatiguing exercise, as well as at 10, 20, and 30 min post-fatigue activity. Sway was measured in both firm and sway-referenced support surface (external perturbation) conditions. Both joint-localized fatigue and overall fatigue were found to induce impairments in postural control, which were further exacerbated by external postural perturbations. Follow-up pairwise comparisons indicated that these impairments persisted at 10 and 30 min post-fatigue. No differences in postural sway were found between fatigue locations or across any interactions between sway and fatigue location. The results indicated that muscular fatigue imposed a prolonged internal perturbation to postural control, regardless of any individual or combined joint fatigue localization. This global effect, combined with the prolonged impairment in postural response, provides support for critical contributions from a central mechanism to postural deficits due to fatigue.     

Minimally invasive technology in the management of breast disease

Minimally invasive surgery is gaining popularity around the world because it achieves the same or even superior results when compared to standard surgery but with less morbidity. Minimally invasive breast surgery is a broad concept encompassing new developments in the field of breast surgery that work on this minimally invasive principle. In this regard, breast-conserving surgery and sentinel lymph node biopsy are good illustrations of this concept. There are three major areas of progress in the minimally invasive management of breast disease. First, percutaneous excisional devices are now available that can replace the surgical excision of breast mass lesions. Second, various ablative treatments are capable of destroying breast cancers in situ instead of surgical excision. Third, mammary ductoscopy provides a new approach to the investigation of mammary duct pathology. Clinical experience and potential applications of these new technologies are reviewed.     

Is homozygous α-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous α-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous a-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.     

若干莽草酸衍生物的合成和生物活性研究

虽然对莽草酸(shikimic acid)的研究由来已久,但只是在陆续发现了具有生物活性的乙二醛酶Ⅰ抑制剂(glyoxalase Ⅰinhibitor 1)和二(口恶)霉素(dioxolamycin 2)等含莽草酸类母核的天然产物后,才有合成莽草酸衍生物进行生物活性研究的报道,即由莽草酸甲酯合成乙二醛酶Ⅰ抑制剂的类似物3。     

The association between retinal ischaemia and end-stage renal damage in thrombotic microangiopathy

Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are conditions in which thrombocytopenia and microangiopathic haemolytic anaemia are associated with organ damage due to thrombotic microangiopathy (TMA). The prognosis for adults with HUS is variable, with some patients presenting with an acute illness from which a full recovery is made, whilst others develop irreversible renal failure. Evidence of retinal ischaemia was noted on presentation in a normotensive patient with irreversible renal failure due to HUS. This study examined prospectively the optic fundi of all patients who subsequently presented to a single adult renal unit (catchment population approximately 700,000) with HUS. Eleven patients presented with HUS over 12 years (1985-1997). Six patients with irreversible renal failure had retinal abnormalities either at the time or within a few days of initial presentation. The other five patients whose renal function recovered did not develop retinal changes during the course of their illness. Retinal ischaemia associated with TMA is a poor prognostic sign in adults with HUS.