Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin

Kaleagasioglu, Ferda; Olcay, Ercan; Olgaç, Vakur

doi:10.1007/s00167-015-3728-z

Cited by 24 publications

(27 citation statements)

References 38 publications

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“…A more compliant membrane/extracellular matrix in statin-treated mice would lower dP/dT. Accordingly, statins cause a deterioration of the biomechanical properties of the Achilles tendon [48] and may be a risk factor for muscle and tendon ruptures and tendinopathies [49, 50]. Statins have thus pleiotropic properties, but the exact mechanism by which they decrease dP/dT requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles

Piette

Dufresne

Frenette

2016

BMC Musculoskelet Disord

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BackgroundCumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles.MethodsAdult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days. At the end of the treatment, the isometric ex vivo contractile properties of the Sol and EDL muscles were measured. Subtetanic and tetanic contractions were assessed and contraction kinetics were recorded. The muscles were then frozen for immunohistochemical analyses. Data were analyzed by two-way ANOVA followed by an a posteriori Tukey’s test.ResultsThe short-term lovastatin treatment did not induce muscle mass loss, muscle fiber atrophy, or creatine kinase (CK) release. It had no functional impact on slow-twitch Sol muscles. However, subtetanic stimulations at 10 Hz provoked greater force production in fast-twitch EDL muscles. The treatment also decreased the maximal rate of force development (dP/dT) of twitch contractions and prolonged the half relaxation time (1/2RT) of tetanic contractions of EDL muscles.ConclusionsAn early short-term statin treatment induced subtle but significant changes in some parameters of the contractile profile of EDL muscles, providing new insights into the selective initiation of statin-induced myopathy in fast-twitch muscles.

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Section: Discussionmentioning

confidence: 99%

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles

Piette

Dufresne

Frenette

2016

BMC Musculoskelet Disord

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“…A preload of 1 N was used to fix the tibia on the device, and a bending force was applied at a speed of 2 mm/min for the test. The strength of the tibia was determined as the maximal force that caused complete failure of the tibia …”

Section: Methodsmentioning

confidence: 99%

“…The strength of the tibia was determined as the maximal force that caused complete failure of the tibia. 17,21…”

Section: Biomechanicsmentioning

confidence: 99%

Comparison of the effects of once‐weekly and once‐daily rhPTH (1–34) injections on promoting fracture healing in rodents

Wen

Zhu

et al. 2017

Journal Orthopaedic Research

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To compare the efficacy of once-weekly and once-daily subcutaneous injections of teriparatide (recombinant human parathyroid hormone 1-34) on fracture healing, 50 adult male Sprague-Dawley rats were subjected to a unilateral tibia fracture and received internal fixation with a Kirschner needle. Based on the injection dose and frequency, the rats were randomly divided into five groups (n = 10 each): subcutaneous injections of saline or 10 µg/kg/w, 20 µg/kg/w, 10 µg/kg/d, and 20 µg/kg/d teriparatide. Four weeks later, the rats were euthanatized, and the fractured tibiae were assessed using X-rays, dual-energy X-ray absorptiometry, micro-computed tomography, the three-point bending biomechanics test, and histology. Compared to the saline control group, either daily or weekly subcutaneous injections of teriparatide significantly increased bone mass, improved the bone microarchitecture, and promoted fracture healing (p < 0.05). There were no significant differences in bone mineral density (BMD), bone microstructure or bone strength between the 20 µg/kg/w and 10 µg/kg/d groups (p > 0.05). Teriparatide 20 µg weekly injections promoted bone fracture healing to the same extent as teriparatide 10 µg daily injections, which can dramatically decrease the cumulative dosage of teriparatide injections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1145-1152, 2018.

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“…A preload of 1 N was used to fix the tibia on the device, and a bending force at a speed of 2 mm/min was applied for the test. The strength of the tibia was determined as the maximal force that caused complete failure of the tibia [22]. …”

Section: Methodsmentioning

confidence: 99%

A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function

et al. 2016

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It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA) injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1–2 weeks. The left tibia received intraosseous injection of a parathyroid hormone 1 receptor (Pth1r) or insulin-like growth factor 1 receptor (Igf-1r) siRNA transfection complex loaded in poloxamer 407 hydrogel, and the right tibia received the same volume of control siRNA. All the tibias received an intraosseous injection of recombinant human parathyroid hormone (1–34) (rhPTH (1–34)) or insulin-like growth factor-1 (IGF-1). Calcein green and alizarin red were injected 6 and 2 days before euthanasia, respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays and immunohistochemistry. Bone mineral density (BMD), microstructure, mineral apposition rates (MARs), and strength were determined by dual-energy X-ray absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and immunohistochemistry results revealed that IGF-1R and PTH1R expression levels were dramatically diminished in the siRNA-treated left tibias compared to the right tibias (both p<0.05). Using poloxamer 407 hydrogel as a controlled-release system prolonged the silencing effect of a single dose of siRNA; the mRNA expression levels of IGF-1R were lower at two weeks than at one week (p<0.01). The BMD, bone microstructure parameters, MAR and bone strength were significantly decreased in the left tibias compared to the right tibias (all p<0.05). This simple and convenient local intraosseous siRNA injection model achieved gene silencing with very small quantities of siRNA over a short treatment period (≤7 days).

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Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin

Cited by 24 publications

References 38 publications

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles

Comparison of the effects of once‐weekly and once‐daily rhPTH (1–34) injections on promoting fracture healing in rodents

A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function

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