Tetsu Yamada

Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase-2/prostaglandin E2 production via CD44 in interleukin-1-stimulated subacromial synovial fibroblasts from patients with rotator cuff disease

A growing body of evidence supports use of intraarticular hyaluronic acid (HA) injection in patients with rotator cuff disease. However, the mechanism of its anti‐inflammatory action has not been clarified. We examined the effects of HA on the expression of mRNAs for proinflammatory cytokines (IL‐1β, IL‐6, and TNF‐α and COX‐2/PGE2 production in IL‐1‐stimulated subacromial‐synovium fibroblasts (SSF) derived from patients with rotator cuff disease. Various concentrations of HA were added to monolayer SSF cultures in the presence of IL‐1β. Gene expression levels were analyzed by quantitative real‐time reverse transcription‐polymerase chain reaction. Intracellular production of COX‐2 was identified by Western blotting. PGE2 concentrations in the culture media were measured by ELISA. CD44 blocking with OS/37 was performed to investigate the mechanism of action of HA. Immunofluorescence cytochemistry confirmed binding of HA and the presence of CD44 on SSF. Exogenous HA significantly and dose‐dependently decreased expression of proinflammatory cytokine mRNAs and COX‐2/PGE2 production in IL‐1‐stimulated SSF. Pretreatment with OS/37 reversed the inhibitory effects of HA. These results provide a basis for explaining why HA is effective for the treatment of rotator cuff disease.

Collagen Production at the Edge of Ruptured Rotator Cuff Tendon is Correlated With Postoperative Cuff Integrity

PURPOSE The purpose was to evaluate the correlation between messenger RNA (mRNA) expression of collagen at the edge of the ruptured rotator cuff tendon and postoperative cuff integrity. METHODS The edge of the ruptured tendon was sampled during open rotator cuff surgery in 12 patients with full-thickness rotator cuff tears (mean age, 58.2 years). The mean period from symptom onset was 9.3 months (range, 1 to 36 months), and the mean tear size was 4.1 cm. As controls, rotator cuff tendons with no gross rupture were taken from 5 fresh cadavers. Production of type I and type III collagen was examined by real-time reverse transcription polymerase chain reaction. By use of magnetic resonance imaging, postoperative cuff integrity was evaluated based on the classification of Sugaya et al. and then scored, ranging from 5 points for type I to 1 point for type V. RESULTS Looking at the mRNA of type I and type III collagen in tendons, we found that the expression of mRNA for both collagen types in ruptured tendons was significantly greater than in control tendons (P = .0462 for type I collagen and P = .0306 for type III collagen). Correlating the mRNA of type I and type III collagen with repaired cuff integrity on postoperative magnetic resonance imaging, we found a close relation between expression of mRNA for both collagen types and postoperative rotator cuff integrity (r = 0.63 [P = .038] for type I collagen and r = 0.626 [P = .03] for type III collagen). Furthermore, expression of type I collagen mRNA showed a significant inverse correlation with the period from symptom onset (r = -0.845, P < .0005). CONCLUSIONS This study showed that expression of mRNA for type I and type III collagen at the edge of the ruptured rotator cuff tendon was significantly correlated with postoperative cuff integrity and that mRNA expression for type I collagen was significantly associated with the period from symptom onset. These results may suggest that conservative treatment should not be prolonged if patients do not respond within a certain period. LEVEL OF EVIDENCE Level III, prognostic case-control study.

Effects of Hyaluronan on Cell Proliferation and mRNA Expression of Procollagens α1 (I) and α1 (III) in Tendon-Derived Fibroblasts from Patients with Rotator Cuff Disease: An in Vitro Study

Background Hyaluronan (HA) improves postoperative recovery after flexor tendon surgery, preventing postoperative adhesion. However, its influence on the rotator cuff tendon after cuff repair has not yet been clarified in detail. Hypothesis Hyaluronan is likely to modulate cell proliferation and mRNA expression of procollagens α1 (I) and α1 (III) in tendon-derived fibroblasts in patients with rotator cuff disease. Study Design Controlled laboratory study. Methods The study subjects were 10 patients with rotator cuff disease, with an average age of 62 years (range, 44-72). Various concentrations of HA (1.0-5.0 mg/mL) were added to monolayer-cultured tendon-derived fibroblasts from these patients. Hyaluronan binding and CD44 expression on the tendon-derived fibroblasts were evaluated by confocal microscopy using fluorescein-conjugated HA and antihuman CD44 antibody (OS/37). Cell proliferation was evaluated by recording changes in cell number. The levels of expression of procollagen α1 (I) and α1 (III) mRNA were measured by real-time reverse transcriptase polymerase chain reaction. Results Immunofluorescence cytochemistry detected constitutive binding of HA and CD44 expression on the tendon-derived cells. Treatment with various concentrations of HA significantly inhibited cell proliferation and decreased the expression level of procollagen α1 (III) mRNA, but not that of procollagen α1 (I) mRNA, in the tendon-derived fibroblasts. Conclusion Hyaluronan modulates cell proliferation and the expression level of procollagen α1 (III) mRNA, but not that of procollagen α1 (I), in fibroblasts from patients with rotator cuff disease. Clinical Relevance Postoperative use of exogenous HA may allow the healing of a repaired rotator cuff tendon with minimal adhesion.

Interleukin-6-induced Activation of Signal Transducer and Activator of Transcription-3 in Ruptured Rotator Cuff Tendon:

The aim of this study was to examine interleukin-6 production and the activation of signal transducer and activator of transcription-3 (STAT3) in ruptured rotator cuff tendon. Specimens of ruptured rotator cuff tendons were analysed using real-time reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemistry. Specimens of co-existing inflammatory subacromial synovia were examined for comparison. The level of interleukin-6 messenger RNA was increased in ruptured rotator cuff tendon as well as in subacromial synovium. Western blot analysis showed constitutive production of activated, phosphorylated STAT3 in ruptured rotator cuff tendon and co-existing subacromial synovium. Immunohistochemical examination detected cells producing interleukin-6, interleukin-6 receptor and phosphorylated STAT3 in ruptured rotator cuff tendon, mainly in proliferative vessels and, to a lesser extent, in tendon fibroblasts around the vessels. This study demonstrates that activation of STAT3 induced by interleukin-6 is promoted mainly by proliferative vessels in ruptured rotator cuff tendon.

Examination of Emergency Orthopaedic Patients at a Major Regional Hospital

We report the realities of our emergency medical treatment, and define problems associated with being a regional hospital. The method of presentation, cause of injury, and the principal complaint were collected and examined. Targeted patients included 5, 992 in total examined mainly by the orthopaedics department. They accounted for 11.9% of 50, 273 patients cases who were sent to our hospital for emergencies.According to our data, 12% of 5, 992 patients required admission to hospital. This number comprises 65% of the total yearly orthopaedics inpatients. We also found 33% of the patients come from the suburbs of Kurume city, reflecting the role of the hospital works well as the major regional hospital.However these are times when the second or the third emergency patients are not treated adequately. This implies, the first (the most urgent) patients are treated urgently white less urgent patients are not treated as well. We suggest adjustment to our medical systems. In the near future we have to examine our hospitals function as well as the needs of the community.After doing this, we may have to adjust our medical care systems.