Full metadata record
DC Field | Value | Language |
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dc.creator | Valdés-Fernández, J. (José) | - |
dc.creator | Lopez, T. (Tania) | - |
dc.creator | Ripalda-Cemboráin, P. (Purificación) | - |
dc.creator | Calvo, I.A. (Isabel A.) | - |
dc.creator | Saez, B. (Borja) | - |
dc.creator | Romero-Torrecilla, J.A. (Juan Antonio) | - |
dc.creator | Aldazabal, J. (Javier) | - |
dc.creator | Muiños-López, E. (Emma) | - |
dc.creator | Montiel-Terrón, V. (Verónica) | - |
dc.creator | Orbe, J. (Josune) | - |
dc.creator | Rodriguez, J.A. (José Antonio) | - |
dc.creator | Paramo, J.A. (José Antonio) | - |
dc.creator | Prosper-Cardoso, F. (Felipe) | - |
dc.creator | Granero-Moltó, F. (Froilán) | - |
dc.date.accessioned | 2021-12-23T11:03:26Z | - |
dc.date.available | 2021-12-23T11:03:26Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Valdés-Fernández, J. (José); Lopez, T. (Tania); Ripalda, P. (P.); et al. "Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice". J Bone Miner Res. 36 (11), 2021, 2203 - 2213 | es_ES |
dc.identifier.issn | 0884-0431 | - |
dc.identifier.uri | https://hdl.handle.net/10171/62689 | - |
dc.description.abstract | The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion | es_ES |
dc.description.sponsorship | This work was supported by funds from Mineco (Ministerio de Asuntos Económicos y Transformación Digital) through Instituto de Salud Carlos III and European Regional Development Funds (PI20/00076 and PI17/00136 to FG-M and ISCIII-RETICS RD16/0011/0005 to FP), European Union Horizon 2020 program (874889, HEALIKICK to FG-M), and Departamento de Desarrollo Económico del Gobierno de Navarra (PC009-010-011 3DMedical and PC073-074-075 3DMedical to FG-M). JV-F and JR-T are supported by a fellowship of the Asociación de Amigos de la Universidad de Navarra. We want to express our gratitude to the Experimental Ophthalmology Laboratory, Clínica Universidad de Navarra, for zymographic assays advice and discussion. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/874889/EU | - |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Bone fracture | es_ES |
dc.subject | Endochondral ossification | es_ES |
dc.subject | Extracellular matrix | es_ES |
dc.subject | Macrophages | es_ES |
dc.subject | MMP-10 | es_ES |
dc.title | Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | 10.1002/jbmr.4403 | es_ES |
dc.description.note | CC BY NC ND | es_ES |
dc.identifier.doi | 10.1002/jbmr.4403 | - |
dadun.citation.endingPage | 2213 | es_ES |
dadun.citation.number | 11 | es_ES |
dadun.citation.publicationName | J Bone Miner Res | es_ES |
dadun.citation.startingPage | 2203 | es_ES |
dadun.citation.volume | 36 | es_ES |
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