Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Surfing the spectrum - what is on the horizon?

Diagnostic imaging techniques have evolved with technological advancements - but how far? The objective of this article was to explore the electromagnetic spectrum to find imaging techniques which may deliver diagnostic information of equal, or improved, standing to conventional radiographs and to explore any developments within radiography which may yield improved diagnostic data. A comprehensive literature search was performed using Medline, Web of Knowledge, Science Direct and PubMed Databases. Boolean Operators were used and key-terms included (not exclusively): terahertz, X-ray, ultraviolet, visible, infra-red, magnetic resonance, dental, diagnostic, caries and periodontal. Radiographic techniques are primarily used for diagnostic imaging in dentistry, and continued developments in X-ray imaging include: phase contrast, darkfield and spectral imaging. Other modalities have potential application, for example, terahertz, laser doppler and optical techniques, but require further development. In particular, infra-red imaging has regenerated interest with caries detection in vitro, due to improved quality and accessibility of cameras. Non-ionising imaging techniques, for example, infra-red, are becoming more commensurate with traditional radiographic techniques for caries detection. Nevertheless, X-rays continue to be the leading diagnostic image for dentists, with improved diagnostic potential for lower radiation dose becoming a reality

IL-1β induces murine airway 5-HT_2Areceptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

<p>Abstract</p> <p>Background</p> <p>Interleukin 1 beta (IL-1β) is found in bronchoalveolar lavage fluids from asthmatic patients and plays an important role in normal immunoregulatory processes but also in pathophysiological inflammatory responses. The present study was designed to investigate if IL-1β could be involved in the development of airway hyperresponsiveness and if transcriptional mechanisms, epithelium contractile factors and mitogen-activated protein kinase (MAPK) pathways are involved in IL-1β effect.</p> <p>Methods</p> <p>The effect of IL-1β on 5-hydroxytryptamine (5-HT) induced bronchoconstriction was evaluated in an <it>in-vitro </it>model for assessment of long-term effects of inflammatory mediators on the airway smooth muscle. Murine tracheal segments were cultured up to 8 days in the absence or presence of IL-1β with subsequent evaluation in a myograph system, along with mRNA quantification, focusing on the role of the epithelium, acetylcholine release, transcriptional mechanisms and MAPK activity.</p> <p>Results</p> <p>During control conditions, 5-HT induced a relatively weak contraction. Presence of IL-1β increased this response in a time- and concentration-dependent way. The increased concentration-effect curves could be shifted rightwards in a parallel manner by ketanserin, a selective 5-HT_2Areceptor antagonist, indicating that the responses are mediated by 5-HT_2Areceptors. The mRNA levels of 5-HT_2Areceptors were not changed as a consequence of the IL-1β treatment and actinomycin D, a general transcriptional inhibitor, failed to affect the contractile response, suggesting a non-transcriptional mechanism behind this phenomenon. Neither the removal of the epithelium nor the addition of atropine affected the IL-1β induced enhancement of 5-HT_2Areceptor-mediated contractile response. Application of inhibitors for c-Jun N-terminal kinase (JNK), p38 and extracellular signal-regulated kinase 1 and 2 (ERK1/2) showed that the signaling pathways for JNK and ERK1/2 dominated only in cultured segments (control) whereas JNK and p38 dominated in segments treated with IL-1β.</p> <p>Conclusion</p> <p>IL-1β induces murine airway hyperresponsiveness, via a non-transcriptional up-regulation of 5-HT_2Areceptor-mediated contractile response. The increase of 5-HT contraction is unrelated to epithelial and cholinergic factors, but is dependent on IL-1β-induced changes of MAPK pathways. The fact that IL-1β can alter airway responses to contractile agents such as 5-HT, via alteration of the intracellular MAPK signal transduction pathways, might provide a new concept for future treatment of asthma.</p