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Downregulation of type I collagen expression in the Achilles tendon by dexamethasone: a controlled laboratory study.

ABSTRACT: BACKGROUND:Spontaneous Achilles tendon rupture associated with long-term dexamethasone (Dex) use has been reported. However, few studies have investigated the potential mechanism. The aim of this study was to evaluate the effects of oral Dex on type I collagen in humans and rats and its association with tendon rupture. METHODS:First, six Achilles tendons from patients who received long-term Dex treatment, and another six normal tendons were harvested for histological evaluation. Secondly, 8-week-old rats (n?=?72) were randomly assigned to a Dex group or a control group. Type I collagen was studied at the mechanical, histological, and molecular levels after 3 and 5?weeks. Tenocytes isolated from normal human and rat tendon were used to investigate the effect of Dex on cellular scale. RESULTS:Histological analysis of human and rat tendon tissue revealed an irregular, disordered arrangement of type I collagen in the Dex group compared with the control group. In addition, In the Dex+ group, type I collagen expression decreased in comparison with the Dex- group in both human and rat tenocytes. The mechanical strength of tendons was significantly reduced in the Dex group (68.87?±?11.07?N) in comparison with the control group (81.46?±?7.62?N, P?=?0.013) after 5?weeks. Tendons in the Dex group were shorter with smaller cross-sectional areas (10.71?±?0.34?mm2, 1.44?±?0.22?mm2, respectively) after 5?weeks than those in the control group (11.13?±?0.50?mm2, P?=?0.050, 2.74?±?0.34?mm2, P?

SUBMITTER: Ge Z

PROVIDER: S-EPMC7038574 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Downregulation of type I collagen expression in the Achilles tendon by dexamethasone: a controlled laboratory study.

Ge Zilu Z Tang Hong H Chen Wan W Wang Yunjiao Y Yuan Chengsong C Tao Xu X Zhou Binghua B Tang Kanglai K

Journal of orthopaedic surgery and research 20200224 1

<h4>Background</h4>Spontaneous Achilles tendon rupture associated with long-term dexamethasone (Dex) use has been reported. However, few studies have investigated the potential mechanism. The aim of this study was to evaluate the effects of oral Dex on type I collagen in humans and rats and its association with tendon rupture.<h4>Methods</h4>First, six Achilles tendons from patients who received long-term Dex treatment, and another six normal tendons were harvested for histological evaluation. S ...[more]

PMID: 32093733

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Project description:PURPOSE AND HYPOTHESIS:Adjuvant intermittent pneumatic compression (IPC) during leg immobilization following Achilles tendon rupture (ATR) has been shown to reduce the risk of deep venous thrombosis. The purpose of this study was to investigate whether IPC can also promote tendon healing. METHODS:One hundred and fifty patients with surgical repair of acute ATR were post-operatively leg immobilized and prospectively randomized. Patients were allocated for 2 weeks of either adjuvant IPC treatment (n = 74) or treatment-as-usual (n = 74) in a plaster cast without IPC. The IPC group received 6 h daily bilateral calf IPC applied under an orthosis on the injured side. At 2 weeks post-operatively, tendon healing was assessed using microdialysis followed by enzymatic quantification of tendon callus production, procollagen type I (PINP) and type III (PIIINP) N-terminal propeptide, and total protein content. 14 IPC and 19 cast patients (control group) consented to undergo microdialysis. During weeks 3-6, all subjects were leg-immobilized in an orthosis without IPC. At 3 and 12 months, patient-reported outcome was assessed using reliable questionnaires (ATRS and EQ-5D). At 12 months, functional outcome was measured using the validated heel-rise test. RESULTS:At 2 weeks post-rupture, the IPC-treated patients exhibited 69% higher levels of PINP in the ruptured Achilles tendon (AT) compared to the control group (p = 0.001). Interestingly, the IPC-treated contralateral, intact AT also demonstrated 49% higher concentrations of PINP compared to the non-treated intact AT of the plaster cast group (p = 0.002). There were no adverse events observed associated with IPC. At 3 and 12 months, no significant (n.s.) differences between the two treatments were observed using patient-reported and functional outcome measures. CONCLUSIONS:Adjuvant IPC during limb immobilization in patients with ATR seems to effectively enhance the early healing response by upregulation of collagen type I synthesis, without any adverse effects. Whether prolonged IPC application during the whole immobilization period can also lead to improved long-term clinical healing response should be further investigated. The healing process during leg immobilization in patients with Achilles tendon rupture can be improved through adjuvant IPC therapy, which additionally prevents deep venous thrombosis. LEVEL OF EVIDENCE:Randomized controlled trial, Level I.

Project description:This paper presents a more systematic study of steady-state and time-resolved autofluorescence spectroscopy of collagen isolated from bovine Achilles tendon. In steady-state fluorescence measurements, the excitation and emission spectra of collagen powder, recorded at different fluorescence excitation and detection wavelengths, were compared with the fluorescence excitation and emission spectra of the amino acids phenylalanine, tyrosine, and tryptophan, as well as with similar spectra for 13 autofluorescent collagen cross-links, which have been identified and described in the literature so far. In time-resolved studies, fluorescence was excited by the pulsed light of different wavelengths, and for each excitation wavelength, fluorescence decay was recorded for several detection wavelengths. Data analysis allowed recovery of the fluorescence decay times for each experimental excitation detection event. The obtained information on the decay times of the measured fluorescent signals was discussed, taking into account the available literature data from similar studies of isolated collagen and collagen-rich tissues. Based on the obtained results, it was found that the shape and position of the measured fluorescence excitation and emission spectra of collagen strongly depend on the emission and excitation wavelengths selected in the measurements. From the recorded excitation and emission bands of collagen, it can be concluded with high probability that there are additional, so far unidentified, collagen cross-links, which can be excited at longer excitation wavelengths. In addition, the collagen excitation spectra were measured at longer emission wavelengths at which the collagen cross-links emit fluorescent light. In addition to the emission spectra obtained for excitation in the deep-UV region, the results of time-resolved fluorescence studies with excitation in the deep-UV region and detection at longer wavelengths suggest that fluorescence excitation energy transfer processes occur from the amino acids to the collagen cross-links, and also between the cross-links themselves.

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Downregulation of type I collagen expression in the Achilles tendon by dexamethasone: a controlled laboratory study.

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Downregulation of type I collagen expression in the Achilles tendon by dexamethasone: a controlled laboratory study.

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