Osteoarthritis associated with estrogen deficiency

Roman‐Blas, Jorge A.; Castañeda, Santos; Largo, Raquel; Herrero‐Beaumont, Gabriel

doi:10.1186/ar2791

Cited by 273 publications

(231 citation statements)

References 117 publications

(166 reference statements)

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“…In their examinations on rabbits, they proved that ovariectomy significantly affects osteoarthrosis, and additional supplies of glucocorticosteroids accelerate its occurrence and increases the scope of the disorder. Examinations conducted in sheep confirmed the results obtained by Roman-Bias et al (2009). Sheep from the PC group were affected with osteoarthrosis at the first level according to the Outerbridger classification, while sheep from the SC group developed degen-erative articular cartilage diseases at the first and second level.…”

Section: Discussionsupporting

confidence: 70%

“…Osteoarthrosis connected with a lack (deficiency) of estrogens was studied by Roman-Bias et al (2009) who disagreed with the statement that -in contrast to other tissues such as the endometrium, mammary gland and brain -articular cartilage tissue is not responsive to estrogens and their deficiency. In their examinations on rabbits, they proved that ovariectomy significantly affects osteoarthrosis, and additional supplies of glucocorticosteroids accelerate its occurrence and increases the scope of the disorder.…”

Section: Discussionmentioning

confidence: 99%

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The experimental osteoporosis in sheep – clinical approach

Kiełbowicz¹,

Piątek²,

Bieżyński³

et al. 2015

Polish Journal of Veterinary Sciences

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The implementation of new methods of oseoporotic therapy requires tests on an animal model. One of the best is the sheep, whose numerous advantages over other models are described in the literature. The aim of this study was induction of osteoporosis using steroids and ovariorectomy methods in sheep and description of the change in parameters with regard to healthy sheep. The study was performed on female "merino" breed sheep divided into three groups: Negative control (NC) healthy animals, positive control (PC) ovariorectomised animals and steroid group (SC) where methylprednisolone was implemented. Blood tests, diagnostic arthroscopy, quantitative computed tomography and X-Ray micro-tomography of bone were carried out. Blood tests revealed a decreased level of estrogens, progesterone and increased parathormone and cortisol levels in the SC group. A decrease in bone turnover markers and an increase in bone resorption markers in all groups were also noted. Diagnostic arthroscopy revealed osteoarthrosis in PC and SC groups. Radiological density tests showed a slight decrease in PC and NC groups whereas there was more than a triple decrease in SC. Results obtained from microCT showed quickly developing osteoporosis in the SC group, which is reflected in numerous parameters analysed in this study. The best effects for osteoporosis induction were obtained using ovariorectomised sheep with methylprednisolone injections.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

The experimental osteoporosis in sheep – clinical approach

Kiełbowicz¹,

Piątek²,

Bieżyński³

et al. 2015

Polish Journal of Veterinary Sciences

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“…Accumulating evidence supports a role of estrogen in adult joint tissues but, similar to ERR␣, estrogen may have dual effects (46,47). For example, reports of the efficacy of estrogen replacement therapy in restoring cartilage in joint tissues in patients with OA are mixed (48,49), possibly reflecting both the proinflammatory and antiinflammatory effects attributed to estrogen (47,50). Furthermore, circulating IL-1␤ levels have been shown to be increased after menopause, and estrogen modulates IL-1␤-induced proteoglycan degradation and de novo expression of MMPs 1, 3, and 13 in chondrocytes (47), activities that parallel ERR␣ regulation of MMP-13.…”

mentioning

confidence: 99%

Estrogen receptor–related receptor α regulation by interleukin‐1β in prostaglandin E₂– and cAMP‐dependent pathways in osteoarthritic chondrocytes

Bonnelye¹,

Reboul²,

Duval³

et al. 2011

Arthritis & Rheumatism

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Objective. We reported previously that the orphan nuclear receptor, estrogen receptor-related receptor ␣ (ERR␣), is expressed in articular chondrocytes and is dysregulated in a mouse model of inflammatory arthritis. The aim of this study, therefore, was to determine whether ERR␣ is also dysregulated in patients with osteoarthritis (OA).Methods. ERR␣ messenger RNA (mRNA) and protein were quantified in normal and OA cartilage samples and in OA chondrocytes in vitro, with and without short-term treatment with a variety of OAassociated factors and signaling pathway agonists and inhibitors.Results. ERR␣ expression was lower in OA than in normal articular cartilage. Interleukin-1␤ (IL-1␤) markedly up-regulated ERR␣ expression in OA chondrocytes in vitro, and agonist or inhibitor treatment indicated that the up-regulation was dependent on cyclooxygenase 2 (COX-2; NS398), prostaglandin E 2 , cAMP (8-bromo-cAMP), and protein kinase A (PKA; KT5720). Treatment with the ERR␣ inverse agonist XCT790 decreased the expression of SOX9 and the up-regulation of ERR␣ by IL-1␤, suggesting autoregulation of ERR␣ in the IL-1␤ pathway. Matrix metalloproteinase 13 (MMP-13) expression was also decreased by treatment with XCT790 plus IL-1␤ versus IL-1␤ alone, and the down-regulation of MMP-13 mRNA and protein observed with XCT790 alone suggests that the up-regulation of MMP-13 by IL-1␤ is ERR␣-dependent.Conclusion. We report the first evidence that ERR␣ expression is regulated by IL-1␤ in COX-2-, cAMP-, and PKA-dependent pathways in OA chondrocytes. We confirmed that SOX9 is an ERR␣ target gene in human, as in rodent, chondrocytes and identified MMP-13 as a potential new target gene, which suggests that ERR␣ may both respond to the healing signal and contribute to extracellular degradation in OA cartilage.Osteoarthritis (OA) is a chronic disease characterized by slowly progressive destruction of the articular cartilage, combined with changes in the synovium and subchondral bone (1). Various estimates suggest that more than 40% of 70-year-old people currently have the disease, ranking OA as the most common arthritic condition. The prevalence and the pain and disability associated with progression of the disease have led to intense interest in defining markers for OA as well as the mechanisms underlying the disease.The cellular component of cartilage is the chondrocyte, and adult articular chondrocytes, although considered quiescent in normal cartilage, can respond to mechanical injury and biologic stimuli such as cytokines and growth factors. Interleukin-1␤ (IL-1␤) is a wellknown proinflammatory cytokine that is implicated in

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“…The dramatic increase in the prevalence of OA in women after menopause 18 , which is associated with the presence of estrogen receptors in articular tissues, suggests a link between OA and loss of ovarian function 18 . Although great attention is focused on estrogen's effect on articular cartilage, its deficiency also affects other joint tissues involved in OA, like subchondral bone, synovium, muscle, ligament and capsule 13 . Since OA is a chronic disease, prevalence measurement becomes much more important than incidence and can indicate the risk of exposure for susceptible individuals.…”

Section: Discussionmentioning

confidence: 99%