Osteonecrosis in a Chemically Induced Rat Model of Human Hemolytic Disorders Associated with Thrombosis ? A New Model for Avascular Necrosis of Bone

Shabat, Shay; Nyska, Abraham; Long, Philip H.; Goelman, G.; Abramovitch, Rinat; Ezov, Nathan; Levin-Harrus, Tal; Peddada, Shyamal D.; Redlich, Meir; Yedgar, Saul; Nyska, Meir

doi:10.1007/s00223-003-0068-7

Cited by 15 publications

(3 citation statements)

References 41 publications

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“…Metabolic activation of 2-butoxyethanol (BE) to form butoxyacetic acid (BAA) is a prerequisite for the development of hematotoxicity. Shabat et al [77] reported a new rat model for ON induced by four daily doses of 250 mg BE/5 ml water/kg of body weight for four consecutive days. At 24 days after induction, ON in femur was seen histologically in 1 of 8 animals while changes in the femurs were confined to the diaphysis.…”

Section: Chemically Induced Onmentioning

confidence: 99%

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Experimental animal models of osteonecrosis

et al. 2011

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Osteonecrosis (ON) or avascular necrosis (AVN) is a common bone metabolic disorder, mostly affecting femoral head. Although many biological, biophysical, and surgical methods have been tested to preserve the femoral head with ON, none has been proven fully satisfactory. It lacks consensus on an optimal approach for treatment. This is due, at least in part, to the lack of ability to systematically compare treatment efficacy using an ideal animal model that mimics full-range osteonecrosis of femoral head (ONFH) in humans with high incidence of joint collapse accompanied by reparative reaction adjacent to the necrotic bone in a reproducible and accessible way. A number of preclinical animal ON models have been established for testing potential efficacy of various modalities developed for prevention and treatment of ON before introduction into clinics for potential applications. This paper describes a number of different methods for creating animal experimental ON models. Advantages and disadvantages of such models are also discussed as reference for future research in battle against this important medical condition.

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Section: Chemically Induced Onmentioning

confidence: 99%

“…Bone injury occurs in human hemolytic disorders associated with thrombosis, such as betathalassemia and sicklecell disease [77]. Metabolic activation of 2-butoxyethanol (BE) to form butoxyacetic acid (BAA) is a prerequisite for the development of hematotoxicity.…”

Section: Chemically Induced Onmentioning

confidence: 99%

Experimental animal models of osteonecrosis

et al. 2011

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“…Cessation or a reduction in blood flow along capillaries could also play an aetiological role in endothelial cell apoptosis. 59 – 61…”

Section: Endothelial Cell Apoptosismentioning

confidence: 99%

Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head

2017

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The two major theories of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) are apoptosis and ischaemia. The traditional theory implicates ischaemia as the main aetiological factor because the final common pathway of ONFH is interruption of blood supply to the bone. The most common causes of interruption of blood supply include fat embolism and coagulation disorders. GCs can directly or indirectly lead to coagulation disorders, producing a hypercoagulable state, followed by poor blood flow, ischaemia, and eventually ONFH. This review summarizes the existing knowledge on coagulation disorders in the context of GC-induced ONFH, including hypofibrinolysis and thrombophilia, endothelial cell dysfunction and damage, endothelial cell apoptosis, lipid metabolism, platelet activation, and the effect of anticoagulant treatment.

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Potential involvement of p53 in ischemia/reperfusion-induced osteonecrosis

et al. 2008

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Idiopathic osteonecrosis of the femoral head (ION) is a devastating pathological condition of unknown etiology. In this study, we developed a simple murine model of osteonecrosis and investigated the underlying molecular mechanisms. In this model, the central portion of the tails of male C57BL/6 mice were tightly ligated to produce ischemic regions at sites distal to the ligatures. The occlusive ligatures were maintained for the indicated periods and then removed to induce reperfusion. The tails were histologically examined, and gene expression was analyzed by PCR array. The effect of p53 expression on osteocytes apoptosis was examined using preosteocytic MLO-A5 cells. In addition, the expression of p53 was analyzed in the femoral head samples obtained from hip osteoarthritis (OA) patients and ION patients. Caudal vertebrae distal to the ligatures (distal region) exhibited histological changes mimicking those observed in ION. Expression of p53 was increased in the distal region, and overexpression of p53 induced apoptosis in MLO-A5 cells. Treatment with a p53 inhibitor suppressed osteocyte apoptosis in the distal region. Strong p53 immunostaining was observed in osteocytes, vascular endothelial cells, and bone marrow cells in the femoral heads from ION patients but not from OA patients. Ischemia/reperfusion of the caudal vertebrae is a useful murine model of osteonecrosis, mimicking the histological changes found in ION. Using this model, we found the possible involvement of p53 in the osteocyte apoptosis observed in ION. Therapeutics targeting p53 might be a useful approach to ameliorating or even preventing osteonecrosis in ION patients.

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Osteonecrosis in a Chemically Induced Rat Model of Human Hemolytic Disorders Associated with Thrombosis ? A New Model for Avascular Necrosis of Bone

Cited by 15 publications

References 41 publications

Experimental animal models of osteonecrosis

Experimental animal models of osteonecrosis

Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head

Potential involvement of p53 in ischemia/reperfusion-induced osteonecrosis

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