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Article ; Online: Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats.

Bagi, Cedo M / Edwards, Kristin / Berryman, Edwin

2017 Volume 102, Issue 6, Page(s) 683–694

Abstract: Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated ...

Abstract	Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure. Our objective was to create a rat model of human metabolic syndrome and determine the long-term impact of early-onset T1D on bone structure and strength in obese growing rats. Male rats were given either standard chow and RO water (Controls) or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and 45% glucose (HFD). A third group of rats received the HFD diet and a single dose of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose tolerance tests were conducted several times during the course of the study. Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated at 10 and 28 weeks. Shear wave elastography and histology were used to assess liver fibrosis. Cancellous bone structure and cortical bone geometry were evaluated by mCT and strength by the 3-point bending method. Body mass and fat accumulation was significantly higher in HFD and HFD/Sz rats compared to Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the change was more severe in diabetic rats. Although both groups of obese rats had larger bones, their cancellous structure and cortical thickness were reduced, resulting in diminished strength that was further aggravated by diabetes. The HFD and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with NASH. Our data provide strong indication that obesity accompanied by type 1 diabetes significantly aggravates comorbidities of MeSy, including the development of osteopenia and weaker bones. The juvenile rat skeleton seems to be more vulnerable to damage imposed by obesity and diabetes and may offer a model to inform the underlying pathology associated with the unusually high fracture rates in obese adults with diabetes.
MeSH term(s)	Animals ; Body Weight/physiology ; Bone Density/physiology ; Bone and Bones/metabolism ; Cholesterol/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diet, High-Fat ; Male ; Metabolic Syndrome/complications ; Metabolic Syndrome/metabolism ; Obesity/complications ; Obesity/metabolism ; Osteoporosis/metabolism ; Rats, Sprague-Dawley
Chemical Substances	Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2017-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-017-0367-z
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Zs.A 317: Show issues

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Article: Targeting of therapeutic agents to bone to treat metastatic cancer.

Bagi, Cedo M

Advanced drug delivery reviews

2005 Volume 57, Issue 7, Page(s) 995–1010

Abstract: The three main organs affected by metastasis of all cancers include lungs, liver, and bone. Clinical confirmation of tumor spread to these organs is a negative prognostic sign that marks the stage when disease is rarely curable. Today, treatment of bone ... ...

Abstract	The three main organs affected by metastasis of all cancers include lungs, liver, and bone. Clinical confirmation of tumor spread to these organs is a negative prognostic sign that marks the stage when disease is rarely curable. Today, treatment of bone metastases is primarily palliative. The aims of treatment are to relieve pain, prevent development of pathologic fractures, improve mobility and function, and if possible, prolong survival. Significant improvements in our understanding of tumor biology along with early tumor detection has led to the discovery of few innovative approaches aimed to treat bone metastases. The most promising treatment modalities include combination of anti-cancer therapies (surgery, radiation therapy, citostatic therapy) with bone antiresorptive therapies (bisphosphonate) that specifically target osteoclasts, bone resorbing cells. The osteoclast, whose increased activity is induced by the tumor, is responsible for the deterioration of bone mass and structure along with the release of grow factors that feed back and support further tumor growth. The current pharmaceutical approach is to target bone metastases by developing drugs that specifically target tumor cells in bone in addition to bone stroma since skeletal metastases are more resistant to treatment, present the highest bulk of tumor mass in the body, serve as site for secondary spread of tumor cells, and are associated with significant morbidity. There is a real need for a more effective modified release of newer anti-cancer drugs such as gene therapy and immunotherapy by using established and novel delivery platforms that will improve therapy and reduce side effects as a result of more appropriate plasma profiles. Overall, however, developments regarding treatment of cancer metastases to bone are encouraging. The scope of future advancements is immense and includes innovative therapeutics and delivery systems aimed to improve skeletal affinity, selectivity, and efficacy of drugs.
MeSH term(s)	Animals ; Bone Neoplasms/pathology ; Bone Neoplasms/secondary ; Bone Neoplasms/therapy ; Breast Neoplasms/pathology ; Clinical Trials as Topic ; Combined Modality Therapy ; Diphosphonates/therapeutic use ; Female ; Genetic Therapy ; Humans ; Immunotherapy ; Male ; Prostatic Neoplasms/pathology ; Selective Estrogen Receptor Modulators/therapeutic use
Chemical Substances	Diphosphonates ; Selective Estrogen Receptor Modulators
Language	English
Publishing date	2005-05-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2004.12.014
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Zs.A 2241: Show issues

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Article: Models of hepatocellular carcinoma and biomarker strategy.

Bagi, Cedo M / Andresen, Catharine J

Cancers

2010 Volume 2, Issue 3, Page(s) 1441–1452

Abstract: The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome ... ...

Abstract	The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.
Language	English
Publishing date	2010-07-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers2031441
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Article: HMG-CoA reductase inhibitors - a review of the recent patent literature.

Bagi, Cedo M

IDrugs : the investigational drugs journal

2002 Volume 5, Issue 3, Page(s) 266–277

Abstract: Statins are very potent inhibitors of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis at the mevalonate level. Today there is an increasing tendency to treat hypercholesterolemia aggressively, hence, the greater use of statins ... ...

Abstract	Statins are very potent inhibitors of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis at the mevalonate level. Today there is an increasing tendency to treat hypercholesterolemia aggressively, hence, the greater use of statins worldwide. The pleiotropic effect of statins is well documented. Examination of the patent literature reveals that in the past year pharmaceutical companies continued to be very active in this area. Accumulated knowledge of the actions of statins shows that they may be involved in many more processes than originally anticipated. Hence, in addition to 'old' indications (hypercholesterolemia, hyperlipidemia and atherosclerosis) many patent applications published in 2001 attempted to cover combination therapies, widening indications for statins to almost all known diseases. Many of the 'new' claims are not well substantiated and biological data are absent. Based on the magnitude of cardiovascular disease and aging population globally this area of drug discovery will continue to be an important area of research for all pharmaceutical companies.
Language	English
Publishing date	2002-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2086568-5
ISSN	2040-3410 ; 1369-7056
ISSN (online)	2040-3410
ISSN	1369-7056
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Zs.A 6320: Show issues

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Article ; Online: Nanoparticle contrast-enhanced micro-CT: A preclinical tool for the 3D imaging of liver and spleen in longitudinal mouse studies.

Liu, Chang-Ning / Morin, Jeffrey / Dokmanovich, Melba / Bluette, Crystal T / Goldstein, Richard / Manickam, Balasubramanian / Bagi, Cedo M

Journal of pharmacological and toxicological methods

2019 Volume 96, Page(s) 67–77

Abstract: In drug discovery and development, X-ray micro-computed tomography (micro-CT) has gained increasing importance over the past decades. In recent years, micro-CT imaging of soft tissues has become popular due to the introduction of a variety of radiopaque ... ...

Abstract	In drug discovery and development, X-ray micro-computed tomography (micro-CT) has gained increasing importance over the past decades. In recent years, micro-CT imaging of soft tissues has become popular due to the introduction of a variety of radiopaque contrast agents. More recently, nanoparticle-based ExiTron nano 12,000 has become commercially available for the nonclinical micro-CT imaging of soft tissues in rodents. Phagocytosis and accumulation of the contrast agent by Kupffer cells in the liver, as well as macrophages in the spleen, increase the soft tissue X-ray attenuation for up to 6 months. Therefore, it is essential to understand the potential toxicity of this nanomaterial in micro-CT imaging prior to its application in pharmacology and/or toxicology studies. Herein, we describe the time-course and distribution of the contrast in the liver, spleen and blood after a single intravenous injection (IV) of this nanoparticle contrast agent at 0.1 ml/mouse. Thoracic images of male adult C57BL/6 mice were acquired using a Bruker SkyScan 1276 micro-CT over a period of 29 days. The stability of X-ray attenuation enhancement in the above tissues was also tested after a single dose of Kupffer cell toxicant gadolinium chloride (GdCl
MeSH term(s)	Animals ; Contrast Media/administration & dosage ; Contrast Media/pharmacokinetics ; Gadolinium/toxicity ; Image Enhancement/methods ; Imaging, Three-Dimensional/methods ; Kidney/diagnostic imaging ; Kidney/metabolism ; Kidney/pathology ; Kupffer Cells/drug effects ; Kupffer Cells/metabolism ; Liver/diagnostic imaging ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Longitudinal Studies ; Male ; Mice ; Mice, Inbred C57BL ; Nanoparticles/administration & dosage ; Nanoparticles/metabolism ; Spleen/diagnostic imaging ; Spleen/metabolism ; Spleen/pathology ; X-Ray Microtomography/instrumentation ; X-Ray Microtomography/methods
Chemical Substances	Contrast Media ; Gadolinium (AU0V1LM3JT) ; gadolinium chloride (P7082WY76D)
Language	English
Publishing date	2019-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2019.02.003
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Zs.A 1440: Show issues

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Article: Nanoparticle contrast-enhanced micro-CT: A preclinical tool for the 3D imaging of liver and spleen in longitudinal mouse studies

Liu, Chang-Ning / Morin, Jeffrey / Dokmanovich, Melba / Bluette, Crystal T. / Goldstein, Richard / Manickam, Balasubramanian / Bagi, Cedo M.

Journal of pharmacological and toxicological methods. 2019 Mar., Apr., v. 96

2019

Abstract	In drug discovery and development, X-ray micro-computed tomography (micro-CT) has gained increasing importance over the past decades. In recent years, micro-CT imaging of soft tissues has become popular due to the introduction of a variety of radiopaque contrast agents. More recently, nanoparticle-based ExiTron nano 12,000 has become commercially available for the nonclinical micro-CT imaging of soft tissues in rodents. Phagocytosis and accumulation of the contrast agent by Kupffer cells in the liver, as well as macrophages in the spleen, increase the soft tissue X-ray attenuation for up to 6 months. Therefore, it is essential to understand the potential toxicity of this nanomaterial in micro-CT imaging prior to its application in pharmacology and/or toxicology studies. Herein, we describe the time-course and distribution of the contrast in the liver, spleen and blood after a single intravenous injection (IV) of this nanoparticle contrast agent at 0.1 ml/mouse. Thoracic images of male adult C57BL/6 mice were acquired using a Bruker SkyScan 1276 micro-CT over a period of 29 days. The stability of X-ray attenuation enhancement in the above tissues was also tested after a single dose of Kupffer cell toxicant gadolinium chloride (GdCl₃) at 15 mg/kg on day 2. The liver, spleen and kidney were examined microscopically on days 15 and 29 post treatment. Serum and liver cytokines (IL-1β, IL-2, IL-6, IL-10, IL-12p70, IFN-γ, IP-10, MIP1-α, MIP1-β and TNF-α) were quantified on days 15 and 29 as indicators of a pro-inflammatory response to treatment. This study determined that there was an accumulation of amphophilic granular material in the cells of the mononuclear phagocyte system in the liver and spleen following a single dose of ExiTron nano 12,000 and a second dose of GdCl₃ or its vehicle. However, ExiTron nano12000 contrast administration did not cause any hepatotoxicity in the liver, nor did pro-inflammatory cytokines release in the liver or serum. Similarly, there were no adverse pathologies in the spleen or kidneys. In summary, ExiTron nano12000 contrast agent-enhanced micro-CT could be used as a safe method in up to 29-day longitudinal efficacy and toxicology mouse studies for the non-invasive assessment of the liver and spleen.
Keywords	X-radiation ; adults ; blood serum ; chlorides ; drugs ; gadolinium ; hepatotoxicity ; inflammation ; interleukin-10 ; interleukin-12 ; interleukin-2 ; interleukin-6 ; intravenous injection ; kidneys ; liver ; males ; mice ; micro-computed tomography ; phagocytosis ; pharmacology ; spleen ; tissues ; toxicology
Language	English
Dates of publication	2019-03
Size	p. 67-77.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2019.02.003
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Effects of Monoclonal Antibodies against Nerve Growth Factor on Healthy Bone and Joint Tissues in Mice, Rats, and Monkeys: Histopathologic, Biomarker, and Microcomputed Tomographic Assessments.

Gropp, Kathryn E / Carlson, Cathy S / Evans, Mark G / Bagi, Cedo M / Reagan, William J / Hurst, Susan I / Shelton, David L / Zorbas, Mark A

Toxicologic pathology

2018 Volume 46, Issue 4, Page(s) 408–420

Abstract: Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a ... ...

Abstract	Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all NGF inhibitors. Three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor muMab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, Sprague-Dawley rats, and C57BL/6 mice. Joint and bone endpoints included histology, immunohistochemistry, microcomputed tomography (mCT) imaging, and serum biomarkers of bone physiology. Responses of bone endpoints to tanezumab were evaluated in monkeys at 4 to 30 mg/kg/week for 26 weeks and in rats at 0.2 to 10 mg/kg twice weekly for 28 days. The effects of muMab911 at 10 mg/kg/week for 12 weeks on selected bone endpoints were determined in mice. Tanezumab and muMab911 had no adverse effects on any bone or joint parameter. There were no test article-related effects on bone or joint histology, immunohistochemistry, or structure. Reversible, higher osteocalcin concentrations occurred only in the rat study. No deleterious effects were observed in joints or bones in monkeys, rats, or mice administered high doses of tanezumab or muMab911.
MeSH term(s)	Animals ; Antibodies, Monoclonal/toxicity ; Antibodies, Monoclonal, Humanized/toxicity ; Bone and Bones/drug effects ; Joints/drug effects ; Macaca fascicularis ; Mice ; Mice, Inbred C57BL ; Nerve Growth Factor/antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Tomography, X-Ray Computed
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Nerve Growth Factor (9061-61-4) ; tanezumab (EQL0E9GCX1)
Language	English
Publishing date	2018-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	841009-4
ISSN	1533-1601 ; 0192-6233
ISSN (online)	1533-1601
ISSN	0192-6233
DOI	10.1177/0192623318772501
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Zs.A 1975: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 473: Show issues

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Article: Comparative bone anatomy of commonly used laboratory animals: implications for drug discovery.

Bagi, Cedo M / Berryman, Edwin / Moalli, Maria R

Comparative medicine

2011 Volume 61, Issue 1, Page(s) 76–85

Abstract: To accommodate functional demands, the composition and organization of the skeleton differ among species. Microcomputed tomography has improved our ability markedly to assess structural parameters of cortical and cancellous bone. The current study ... ...

Abstract	To accommodate functional demands, the composition and organization of the skeleton differ among species. Microcomputed tomography has improved our ability markedly to assess structural parameters of cortical and cancellous bone. The current study describes differences in cortical and cancellous bone structure, bone mineral density, and morphology (geometry) at the proximal femur, proximal femoral diaphysis, lumbar vertebrae, and mandible in mice, rats, rabbits, dogs, and nonhuman primates. This work enhances our understanding of bone gross and microanatomy across lab animal species and likely will enable scientists to select the most appropriate species and relevant bone sites for research involving skeleton. We evaluated the gross and microanatomy of the femora head and neck, lumbar spine, and mandible and parameters of cancellous bone, including trabecular number, thickness, plate separation, and connectivity among species. The skeletal characteristics of rabbits, including a very short femoral neck and small amounts of cancellous bone at the femoral neck, vertebral body, and mandible, seem to make this species the least desirable for preclinical research of human bone physiology; in comparison, nonhuman primates seem the most applicable for extrapolation of data to humans. However, rodent (particularly rat) models are extremely useful for conducting basic research involving the skeleton and represent reliable and affordable alternatives to dogs and nonhuman primates. Radiology and microcomputed tomography allow for reliable evaluation of bone morphology, microarchitecture, and bone mineral density in preclinical and clinical environments.
MeSH term(s)	Animals ; Bone Density ; Diaphyses/anatomy & histology ; Diaphyses/diagnostic imaging ; Dogs ; Drug Discovery ; Femur/anatomy & histology ; Femur/diagnostic imaging ; Lumbar Vertebrae/anatomy & histology ; Lumbar Vertebrae/diagnostic imaging ; Macaca fascicularis/anatomy & histology ; Mandible/anatomy & histology ; Mandible/diagnostic imaging ; Mice ; Rabbits ; Rats ; X-Ray Microtomography
Language	English
Publishing date	2011-08-08
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2006425-1
ISSN	1532-0820 ; 0023-6764
ISSN	1532-0820 ; 0023-6764
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Zs.B 601: Show issues

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Article: Comparative Bone Anatomy of Commonly Used Laboratory Animals: Implications for Drug Discovery

Bagi, Cedo M / Berryman, Edwin / Moalli, Maria R

Comparative medicine. 2011 Feb., v. 61, no. 1

2011

Abstract	To accommodate functional demands, the composition and organization of the skeleton differ among species. Microcomputed tomography has improved our ability markedly to assess structural parameters of cortical and cancellous bone. The current study describes differences in cortical and cancellous bone structure, bone mineral density, and morphology (geometry) at the proximal femur, proximal femoral diaphysis, lumbar vertebrae, and mandible in mice, rats, rabbits, dogs, and nonhuman primates. This work enhances our understanding of bone gross and microanatomy across lab animal species and likely will enable scientists to select the most appropriate species and relevant bone sites for research involving skeleton. We evaluated the gross and microanatomy of the femora head and neck, lumbar spine, and mandible and parameters of cancellous bone, including trabecular number, thickness, plate separation, and connectivity among species. The skeletal characteristics of rabbits, including a very short femoral neck and small amounts of cancellous bone at the femoral neck, vertebral body, and mandible, seem to make this species the least desirable for preclinical research of human bone physiology; in comparison, nonhuman primates seem the most applicable for extrapolation of data to humans. However, rodent (particularly rat) models are extremely useful for conducting basic research involving the skeleton and represent reliable and affordable alternatives to dogs and nonhuman primates. Radiology and microcomputed tomography allow for reliable evaluation of bone morphology, microarchitecture, and bone mineral density in preclinical and clinical environments.
Keywords	Primates ; bone density ; dogs ; drugs ; femur ; humans ; laboratory animals ; lumbar spine ; mice ; micro-computed tomography ; models ; physiology ; rabbits ; radiology ; rats ; skeleton ; vertebrae
Language	English
Size	p. 76-85.
Document type	Article
ISSN	1532-0820
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Correlation between μCT imaging, histology and functional capacity of the osteoarthritic knee in the rat model of osteoarthritis.

Bagi, Cedo M / Zakur, David E / Berryman, Edwin / Andresen, Catharine J / Wilkie, Dean

Journal of translational medicine

2015 Volume 13, Page(s) 276

Abstract: Background: To acquire the most meaningful understanding of human arthritis, it is essential to select the disease model and methodology translatable to human conditions. The primary objective of this study was to evaluate a number of analytic ... ...

Abstract	Background: To acquire the most meaningful understanding of human arthritis, it is essential to select the disease model and methodology translatable to human conditions. The primary objective of this study was to evaluate a number of analytic techniques and biomarkers for their ability to accurately gauge bone and cartilage morphology and metabolism in the medial meniscal tear (MMT) model of osteoarthritis (OA). Methods: MMT surgery was performed in rats to induce OA. A dynamic weight bearing system (DWB) system was deployed to evaluate the weight-bearing capacity of the front and hind legs in rats. At the end of a 10-week study cartilage pathology was evaluated by micro computed tomography (μCT), contrast enhanced μCT (EPIC μCT) imaging and traditional histology. Bone tissue was evaluated at the tibial metaphysis and epiphysis, including the subchondral bone. Histological techniques and dynamic histomorphometry were used to evaluate cartilage morphology and bone mineralization. Results: The study results showed a negative impact of MMT surgery on the weight-bearing capacity of the operated limb. Surgery caused severe and extensive deterioration of the articular cartilage at the medial tibial plateau, as evidenced by elevated CTX-II in serum, EPIC μCT and histology. Bone analysis by μCT showed thickening of the subchondral bone beneath the damaged cartilage, loss of cancellous bone at the metaphysis and active osteophyte formation. Conclusions: The study emphasizes the need for using various methodologies that complement each other to provide a comprehensive understanding of the pathophysiology of OA at the organ, tissue and cellular levels. Results from this study suggest that use of histology, μCT and EPIC μCT, and functional DWB tests provide powerful combination to fully assess the key aspects of OA and enhance data interpretation.
MeSH term(s)	Animals ; Disease Models, Animal ; Male ; Osteoarthritis, Knee/diagnostic imaging ; Osteoarthritis, Knee/pathology ; Osteoarthritis, Knee/physiopathology ; Rats ; Rats, Inbred Lew ; X-Ray Microtomography
Language	English
Publishing date	2015-08-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-015-0641-7
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