New Surgical Model for Bone–Muscle Injury Reveals Age and Gender-Related Healing Patterns in the 5 Lipoxygenase (5LO) Knockout Mouse

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversity of Texas at Arlington-
Autor(es): dc.contributorUniversidade Do Sagrado Coração-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorBiguetti, Claudia Cristina [UNESP]-
Autor(es): dc.creatorCouto, Maira Cristina Rondina-
Autor(es): dc.creatorSilva, Ana Claudia Rodrigues [UNESP]-
Autor(es): dc.creatorShindo, João Vitor Tadashi Cosin-
Autor(es): dc.creatorRosa, Vinicius Mateus [UNESP]-
Autor(es): dc.creatorShinohara, André Luis-
Autor(es): dc.creatorAndreo, Jesus Carlos-
Autor(es): dc.creatorDuarte, Marco Antonio Hungaro-
Autor(es): dc.creatorWang, Zhiying-
Autor(es): dc.creatorBrotto, Marco-
Autor(es): dc.creatorMatsumoto, Mariza Akemi [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:27:00Z-
Data de disponibilização: dc.date.available2022-02-22T00:27:00Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-08-11-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3389/fendo.2020.00484-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/199302-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/199302-
Descrição: dc.descriptionSignaling lipid mediators released from 5 lipoxygenase (5LO) pathways influence both bone and muscle cells, interfering in their proliferation and differentiation capacities. A major limitation to studying inflammatory signaling pathways in bone and muscle healing is the inadequacy of available animal models. We developed a surgical injury model in the vastus lateralis (VL) muscle and femur in 129/SvEv littermates mice to study simultaneous musculoskeletal (MSK) healing in male and female, young (3 months) and aged (18 months) WT mice compared to mice lacking 5LO (5LOKO). MSK defects were surgically created using a 1-mm punch device in the VA muscle followed by a 0.5-mm round defect in the femur. After days 7 and 14 post-surgery, the specimens were removed for microtomography (microCT), histopathology, and immunohistochemistry analyses. In addition, non-injured control skeletal muscles along with femur and L5 vertebrae were analyzed. Bones were microCT phenotyped, revealing that aged female WT mice presented reduced BV/TV and trabecular parameters compared to aged males and aged female 5LOKO mice. Skeletal muscles underwent a customized targeted lipidomics investigation for profiling and quantification of lipid signaling mediators (LMs), evidencing age, and gender related-differences in aged female 5LOKO mice compared to matched WT. Histological analysis revealed a suitable bone-healing process with osteoid deposition at day 7 post-surgery, followed by woven bone at day 14 post-surgery, observed in all young mice. Aged WT females displayed increased inflammatory response at day 7 post-surgery, delayed bone matrix maturation, and increased TRAP immunolabeling at day 14 post-surgery compared to 5LOKO females. Skeletal muscles of aged animals showed higher levels of inflammation in comparison to young controls at day 14 post-surgery; however, inflammatory process was attenuated in aged 5LOKO mice compared to aged WT. In conclusion, this new model shows that MSK healing is influenced by age, gender, and the 5LO pathway, which might serve as a potential target to investigate therapeutic interventions and age-related MSK diseases. Our new model is suitable for bone–muscle crosstalk studies.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionNational Institutes of Health-
Descrição: dc.descriptionDepartment of Basic Sciences School of Dentistry São Paulo State University (UNESP-
Descrição: dc.descriptionBone-Muscle Research Center College of Nursing and Health Innovation University of Texas at Arlington-
Descrição: dc.descriptionDepartment of Health Sciences Universidade Do Sagrado Coração-
Descrição: dc.descriptionBauru School of Dentistry University of São Paulo-
Descrição: dc.descriptionDepartment of Basic Sciences School of Dentistry São Paulo State University (UNESP-
Descrição: dc.descriptionFAPESP: #13/04714-8-
Descrição: dc.descriptionFAPESP: 2018/08913-
Descrição: dc.descriptionFAPESP: 2018/19406-0-
Descrição: dc.descriptionNational Institutes of Health: PO1 AG039355-
Descrição: dc.descriptionNational Institutes of Health: R01AG056504-
Descrição: dc.descriptionNational Institutes of Health: R01AG060341-
Idioma: dc.languageen-
Relação: dc.relationFrontiers in Endocrinology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject5 lipoxygenase-
Palavras-chave: dc.subjectaging-
Palavras-chave: dc.subjectbone-
Palavras-chave: dc.subjectlipid mediators-
Palavras-chave: dc.subjectmuscle-
Palavras-chave: dc.subjecttissue healing-
Título: dc.titleNew Surgical Model for Bone–Muscle Injury Reveals Age and Gender-Related Healing Patterns in the 5 Lipoxygenase (5LO) Knockout Mouse-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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