Increased expression of IL-6 family members in tendon pathology.

OBJECTIVES: Histological examination of pathological tendon generally does not reveal signs of inflammation. However, the inflammatory cytokine IL-6 has been shown to be expressed in ruptured rotator cuff tendon. The aim of this study was to investigate the expression of IL-6 family members in painful posterior tibialis tendon (PTT) and in painful and ruptured Achilles tendon (AT) compared with normal tendon. METHODS: AT samples were obtained from cadavers (normal) or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. PTT samples were obtained from patients undergoing surgery for other reasons (normal) and from patients with PTT dysfunction (painful). Total RNA was extracted and mRNA expression was analysed by quantitative real-time PCR. RESULTS: Collagen type I α-chain I (COL1A1) expression was increased in both painful PTT and AT compared with normal. Ciliary neurotrophic factor levels were increased in painful PTT only. In the painful AT, cyclooxygenase-2 (COX2) and IL-6 expression increased compared with normal. In the ruptured AT, levels of VEGF A, COX2, oncostatin-M, leukaemia inhibitory factor and IL-6 expression were higher compared with both normal and painful AT. IL-6R expression decreased in both painful and ruptured AT compared with normal. CONCLUSION: Painful AT and PTT show different expression patterns, indicating a substantial difference between those two tendinopathies. Inflammatory markers are up-regulated in painful and particularly in ruptured AT, pointing towards a role of inflammation not only in rupture healing, but also in Achilles tendinopathy.

Estrogen receptor expression in posterior tibial tendon dysfunction: a pilot study.

BACKGROUND: The pathophysiology of posterior tibial tendon dysfunction (PTTD) is poorly understood. It has been theorized that changes in hormone physiology may be a factor influencing tendon health. Estrogen's influence on the fibroblast has been studied in other musculoskeletal tissues. Gender differences in anterior cruciate ligament (ACL) injuries have been studied and it has been discovered that the Estrogen receptor (ER) as well as Progesterone receptor (PR) are expressed in the ACL. MATERIAL AND METHODS: Eight patients with PTTD requiring surgery were enrolled in our pilot study. The mean patient age was 52.4 (range, 18 to 73) years. There were five female and three male patients. Tendon samples were harvested from diseased PTT. Tendon samples harvested from healthy PTT and healthy flexor digitorum longus (FDL) tendon were used as controls. Tendon samples were processed using specific protocols for total RNA isolation from hypocellular, dense connective tissues. ERα and ERß transcripts were quantified using real time RT-PCR. Quantitative values were obtained from the threshold cycle (Ct) number at which the increase in fluorescent signal associated with an exponential increase of PCR products can be detected. RESULTS: Transcripts of both ERα and ERß were reproducibly detected in RNA samples isolated from our tendon samples. There was no difference in receptor expression between diseased and control tendon samples. There was no difference in receptor expression between male and female patients. CONCLUSION: We found that the tenocyte of the PTT and FDL tendons express ERα and ERß. Normal and diseased tendons of both male and female patients expressed both estrogen receptors. CLINICAL RELEVANCE: Identifying ERα and ERß gene expression in the fibroblast was an initial step in discovering whether tenocytes are targets for estrogen function. Estrogen receptors were identified indirectly by measuring receptor gene expression but we were unable to show a significant difference between diseased and control tendons.

Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture.

INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95% of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.

Changes in collagen matrix composition in human posterior tibial tendon dysfunction.

OBJECTIVE: To investigate whether tendon degeneration in posterior tibial tendon dysfunction syndrome is associated with changes in extracellular matrix collagen composition. METHODS: Specimens from grossly abnormal tendon regions from 9 patients with posterior tibial tendon dysfunction syndrome were prepared for routine histology. Collagens I, III and V were typed by immunoblotting and quantified by densitometry after SDS-PAGE. Proline and hydroxyproline residues were determined by liquid chromatography. Four other samples from grossly normal homologous tendon regions and one surgical specimen from a healthy patient undergoing arthrodesis of the ankle after an accident were included as control. RESULTS: In the grossly abnormal surgical posterior tibial tendon specimens we observed three types of histopathologic conditions present to varying degrees: increased mucin content, fibroblast hypercellularity and neovascularization. Analysis of degenerate tendons demonstrated a 79.3% increase in total proline and a 32.4% increase in 4-hydroxyproline. In addition, damaged tissue contained a higher proportion of collagen type III (mean increase: 53.6%) associated with a concomitant increase in type V collagen (mean increase: 26.4%). These alterations were accompanied by a reduction in type I collagen (mean decrease: 41.4%). CONCLUSIONS: In posterior tibial tendon dysfunction syndrome, the degenerative process results from marked changes in both structural organization and molecular composition of matrix collagens. The higher proportion of type V and type IlI collagens in degenerated tendons is likely to contribute to a decrease in the mechanical resistance of the tissue.

Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture

INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95 percent of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.