Different doses of strontium ranelate and mechanical vibration modulate distinct responses in the articular cartilage of ovariectomized rats

Mierzwa, Aline Gomes Hidalgo; Campos, Jenifer Freitas; Jesus, Marinalva S.; Nader, Helena B.; Lazaretti-Castro, Marise; Reginato, Rejane Daniele

doi:10.1016/j.joca.2017.02.793

Cited by 19 publications

(11 citation statements)

References 49 publications

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“…The expression of MMP-9 was not altered with the use of SrRan. Contrary to what was found in a previous study, no reduction in TNF-α expression was observed in this study ( 33 ).…”

Section: Discussioncontrasting

confidence: 99%

“…Oophorectomy has also been used for the induction of osteoporosis and osteoarthritis in rats by establishing early menopause. Either 300 or 625 mg·kg −1 ·day −1 of SrRan associated with vibratory stimuli, or not, were used for histological investigation of articular cartilage quality, as well as immunohistochemical analysis for caspase-3, collagen type II, TNF-α, and MMP-9 ( 33 ). It is worth mentioning that the expression of caspase-3 is related to cellular apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Rodrigues

Freire

Bonfim

et al. 2018

Braz J Med Biol Res

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Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

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“…The expression of MMP-9 was not altered with the use of SrRan. Contrary to what was found in a previous study, no reduction in TNF-α expression was observed in this study ( 33 ).…”

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Rodrigues

Freire

Bonfim

et al. 2018

Braz J Med Biol Res

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“…A decrease in the expression of TNF-α without changes in leukocyte count and IL-1β levels was also observed in another pre-clinical study of periarticular tissue samples, with lower doses of SrRan (up to 50 mg/kg/day) ( Alves et al, 2017 ). These results were not confirmed in a study with rats subjected to oophorectomy and treated with SrRan at doses of 300 and 625 mg/kg/day, with no reduction of TNF-α and MMPs, which are metal-dependent endopeptidases that remodel the extracellular matrix ( Mierzwa et al, 2017 ).…”

Section: Discussionmentioning

confidence: 94%

“…In rats subjected to oophorectomy, SrRan at doses of 300 mg/kg/day effectively attenuated the progression of OA, improving the quality of cartilaginous matrix by directly stimulating the synthesis of proteoglycans Furthermore, the cellular viability in those animals was preserved, with lower OARSI scores and reduced expression of caspase-3, an enzyme associated with apoptosis. This effect was abrogated with daily doses of 625 mg/kg associated with mechanical vibration ( Mierzwa et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…In line with the current trend of investigating drugs that can control the inflammatory component of OA, pre-clinical studies with SrRan have been performed to test its possible effect in this setting. However, results showing the probable antinociceptive effects of SrRan have conflicted with those of alterations in levels of inflammatory mediators such as TNF-α and IL1-β ( Nunes et al, 2015 ; Alves et al, 2017 ; Mierzwa et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis

et al. 2018

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Introduction: Strontium ranelate (SrRan) has the potential to interfere in the progression of osteoarthritis (OA), multifactorial disease associated with mechanical problems and articular inflammatory changes.Objectives: This study aimed to test the effects of prophylactic and therapeutic use of SrRan on clinical parameters of pain, the inflammatory process, and degradation of the articular cartilage.Methods: This was an experimental study, using a model of knee OA induced by intra-articular injection of monoiodoacetate. Thirty Wistar rats were divided into five groups and treated as indicated: control, without intervention; prophylactic, received SrRan at a daily oral dose of 250 mg/kg for 28 days before OA induction; SrRan treatments, administered 250 or 500 mg/kg/day for 28 days after the induction; and model control, received saline solution after the induction. Behavioral tests (joint incapacity, mechanical hyperalgesia, tactile sensitivity, and forced ambulation), histological evaluation of articular cartilage, and determination of inflammatory cytokines in the synovial fluid (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-α, and interferon [INF]-γ) were performed.Results: Both prophylactic and therapeutic treatments improved the articular discomfort. A prophylactic dose of 500 mg/kg/day also improved mechanical hyperalgesia and the same dose was beneficial on tactile sensitivity. SrRan did not improve ambulation. Levels of IL-6, IL-10, TNF-α, and IFN-γ in SrRan-treated groups with OA were not significantly different compared with those in the normal control animals. The histopathological evaluation showed less articular damage in the SrRan-treated and control groups compared to the saline-treated group.Conclusion: The prophylactic and therapeutic administration of SrRan was associated with improved behavioral patterns of pain, especially joint discomfort. SrRan administration mitigated histological changes in the articular cartilage and reduced the inflammatory process, which beneficially reduced the progression of OA in the experimental model studied.

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Models of Disease

Jiménez

López‐Ruiz

Antich

et al. 2018

Advances in Experimental Medicine and Biology

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Osteochondral (OC) lesions are a major cause of chronic musculoskeletal pain and functional disability, which reduces the quality of life of the patients and entails high costs to the society. Currently, there are no effective treatments, so in vitro and in vivo disease models are critically important to obtain knowledge about the causes and to develop effective treatments for OC injuries. In vitro models are essential to clarify the causes of the disease and the subsequent design of the first barrier to test potential therapeutics. On the other hand, in vivo models are anatomically more similar to humans allowing to reproduce the pattern and progression of the lesion in a controlled scene and offering the opportunity to study the symptoms and responses to new treatments. Moreover, in vivo models are the most suitable preclinical model, being a fundamental and a mandatory step to ensure the successful transfer to clinical trials. Both in vitro and in vitro models have a number of advantages and limitation, and the choice of the most appropriate model for each study depends on many factors, such as the purpose of the study, handling or the ease to obtain, and cost, among others. In this chapter, we present the main in vitro and in vivo OC disease models that have been used over the years in the study of origin, progress, and treatment approaches of OC defects.

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Different doses of strontium ranelate and mechanical vibration modulate distinct responses in the articular cartilage of ovariectomized rats

Abstract: SrR and vibration modulate distinct responses in cartilage. Combined treatment accelerates degeneration. In contrast, SrR treatment at 300 mg/kg/day attenuates osteoarthritis (OA) progression, improving cartilage matrix quality and preserving cell viability in ovariectomized rats.

Cited by 19 publications

References 49 publications

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis

Models of Disease

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