In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology
Abstract Background Haemophilic arthropathy is a chronic and debilitating joint disease caused by recurrent spontaneous joint bleeds in patients with haemophilia. Understanding how characteristics of individual joint bleeds relate to the subsequent development of arthropathy could improve management...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | BMC Musculoskeletal Disorders |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12891-020-03267-5 |
| _version_ | 1818943136339066880 |
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| author | K. K. Vøls M. Kjelgaard-Hansen C. D. Ley A. K. Hansen M. Petersen |
| author_facet | K. K. Vøls M. Kjelgaard-Hansen C. D. Ley A. K. Hansen M. Petersen |
| author_sort | K. K. Vøls |
| collection | DOAJ |
| description | Abstract Background Haemophilic arthropathy is a chronic and debilitating joint disease caused by recurrent spontaneous joint bleeds in patients with haemophilia. Understanding how characteristics of individual joint bleeds relate to the subsequent development of arthropathy could improve management and prevention of this joint disease. Here, we aimed to explore relations between joint bleed characteristics and development of bone pathology in a mouse model of haemophilic arthropathy by using novel in vivo imaging methodology. Methods We characterised induced knee bleeds in a murine model of haemophilic arthropathy by quantitative in vivo fluorescence molecular tomography (FMT) and by measurements of changes in the diameter of the injured knee. Wild-type mice and non-injured haemophilic mice acted as controls. Development of arthropathy was characterised by post mortem evaluation of bone pathology by micro-CT 14 days after bleed-induction. In an in vitro study, we assessed the effect of blood on the quantification of fluorescent signal with FMT. Results In most injured haemophilic mice, we observed significant loss of trabecular bone, and half of the mice developed pathological bone remodelling. Development of pathological bone remodelling was associated with significantly increased fluorescent signal and diameter of the injured knee just 1 day after induction of the bleed. Further, a correlation between the fluorescent signal 1 day after induction of the bleed and loss of trabecular bone reached borderline significance. In the in vitro study, we found that high concentrations of blood significantly decreased the fluorescent signal. Conclusion Our results add novel insights on the pathogenesis of haemophilic arthropathy and underline the importance of the acute phase of joint bleeds for the subsequent development of arthropathy. |
| first_indexed | 2024-12-20T07:22:32Z |
| format | Article |
| id | doaj.art-814b9020ea574b0d94c672dca9f3114c |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-12-20T07:22:32Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-814b9020ea574b0d94c672dca9f3114c2022-12-21T19:48:39ZengBMCBMC Musculoskeletal Disorders1471-24742020-04-0121111010.1186/s12891-020-03267-5In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathologyK. K. Vøls0M. Kjelgaard-Hansen1C. D. Ley2A. K. Hansen3M. Petersen4Global Drug Discovery, Novo Nordisk A/SVeterinary Clinical Sciences, University of CopenhagenGlobal Drug Discovery, Novo Nordisk A/SVeterinary and Animal Sciences, University of CopenhagenGlobal Drug Discovery, Novo Nordisk A/SAbstract Background Haemophilic arthropathy is a chronic and debilitating joint disease caused by recurrent spontaneous joint bleeds in patients with haemophilia. Understanding how characteristics of individual joint bleeds relate to the subsequent development of arthropathy could improve management and prevention of this joint disease. Here, we aimed to explore relations between joint bleed characteristics and development of bone pathology in a mouse model of haemophilic arthropathy by using novel in vivo imaging methodology. Methods We characterised induced knee bleeds in a murine model of haemophilic arthropathy by quantitative in vivo fluorescence molecular tomography (FMT) and by measurements of changes in the diameter of the injured knee. Wild-type mice and non-injured haemophilic mice acted as controls. Development of arthropathy was characterised by post mortem evaluation of bone pathology by micro-CT 14 days after bleed-induction. In an in vitro study, we assessed the effect of blood on the quantification of fluorescent signal with FMT. Results In most injured haemophilic mice, we observed significant loss of trabecular bone, and half of the mice developed pathological bone remodelling. Development of pathological bone remodelling was associated with significantly increased fluorescent signal and diameter of the injured knee just 1 day after induction of the bleed. Further, a correlation between the fluorescent signal 1 day after induction of the bleed and loss of trabecular bone reached borderline significance. In the in vitro study, we found that high concentrations of blood significantly decreased the fluorescent signal. Conclusion Our results add novel insights on the pathogenesis of haemophilic arthropathy and underline the importance of the acute phase of joint bleeds for the subsequent development of arthropathy.http://link.springer.com/article/10.1186/s12891-020-03267-5Haemophilia aHaemophilic arthropathyMouse modelIn vivo imagingFluorescence molecular tomographyMicro-CT |
| spellingShingle | K. K. Vøls M. Kjelgaard-Hansen C. D. Ley A. K. Hansen M. Petersen In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology BMC Musculoskeletal Disorders Haemophilia a Haemophilic arthropathy Mouse model In vivo imaging Fluorescence molecular tomography Micro-CT |
| title | In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology |
| title_full | In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology |
| title_fullStr | In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology |
| title_full_unstemmed | In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology |
| title_short | In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology |
| title_sort | in vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice link between bleeding characteristics and development of bone pathology |
| topic | Haemophilia a Haemophilic arthropathy Mouse model In vivo imaging Fluorescence molecular tomography Micro-CT |
| url | http://link.springer.com/article/10.1186/s12891-020-03267-5 |
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