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101.
Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice
José Valdés-Fernández Tania López-Martínez Purificación Ripalda-Cemboráin Isabel A Calvo Borja Sáez Juan Antonio Romero-Torrecilla Javier Aldazabal Emma Muiños-López Verónica Montiel Josune Orbe José Antonio Rodríguez José Antonio Páramo Felipe Prósper Froilán Granero-Moltó 《Journal of bone and mineral research》2021,36(11):2203-2213
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. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). 相似文献
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Dadi Helgason Solveig Helgadottir Anders Ahlsson Jarmo Gunn Vibeke Hjortdal Emma C. Hansson Anders Jeppsson Ari Mennander Shahab Nozohoor Igor Zindovic Christian Olsson Stefan Orri Ragnarsson Martin I. Sigurdsson Arnar Geirsson Tomas Gudbjartsson 《The Annals of thoracic surgery》2021,111(4):1292-1298
104.
Josefine Jnsson Kristina M. Renault Sonia García-Calzn Alexander Perfilyev Angela C. Estampador Kirsten Nrgaard Mads Vendelbo Lind Allan Vaag Line Hjort Kim F. Michaelsen Emma Malchau Carlsen Paul W. Franks Charlotte Ling 《Diabetes》2021,70(4):854
Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth. 相似文献
105.
Gareth Crouch Nitesh D Dhanekula Karen Byth Emma Burn Sue Lynn Lau Lillias Nairn Liza Nery Jean Doyle Edward Graham Andrew Ellis Roderick J Clifton-Bligh Christian M Girgis 《Journal of bone and mineral research》2021,36(5):910-920
Atypical femur fractures (AFF) are a rare but serious complication of long-term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width <37 mm) + (lateral cortical width at lesser trochanter ≥5 mm), (score, 0 to 3). In an independent validation set of 53 female patients at a different centre in Sydney, a score ≥2 demonstrated 73.3% sensitivity and 69.6% specificity for AFF (area under the receiver-operating characteristic curve [AUC] 0.775, SE 0.063) and remained independently associated with AFF after adjustment for bisphosphonate use. The Sydney AFF score provides a quantitative means of flagging female patients with atraumatic femur fractures who have sustained an AFF as opposed to a TFF. This distinction has clear management implications and may augment current ASBMR diagnostic criteria. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
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108.
Antonio Grande-Trillo Carmen Baliellas Laura Lladó Carlos Casasnovas Joaquín V. Franco-Baux Laura Gracia-Sánchez Miguel Á. Gómez-Bravo Emma González-Vilatarsana Luis Caballero-Gullón Eduardo Echeverri José González-Costello 《American journal of transplantation》2021,21(1):372-381
Domino liver transplantation (DLT) has been used widely in patients with hereditary amyloid transthyretin (ATTR) amyloidosis. New-onset polyneuropathy in recipients of DLT has been reported, but there are few cases of cardiac involvement reported. We aimed to perform a cross-sectional study for ATTR amyloidosis with cardiomyopathy (ATTR-CM) in DLT recipients. We evaluated 23 living DLT recipients a median of 9 years since DLT at 2 referral centers with a systematic cardiac evaluation, including bone scintigraphy. Median age was 72 years, 91% had hypertension, 35% had diabetes mellitus, 67% had chronic renal failure, and 8 patients (35%) developed new-onset polyneuropathy. Only 13% had a normal electrocardiogram and a normal echocardiography, and most of them showed some conduction disturbance or increase in left ventricular wall thickness, but only 1 patient with a Glu89Lys mutation developed ATTR-CM diagnosed by bone scintigraphy and endomyocardial biopsy. None of the recipients of a DLT with Val30Met mutation showed cardiac involvement by bone scintigraphy. In conclusion, DLT from Val30Met donors seems to be safe regarding the development of ATTR-CM. Evaluation of cardiomyopathy in DLT recipients is challenging due to concomitant comorbidities and in this context, bone scintigraphy can be helpful to evaluate ATTR-CM. 相似文献
109.
Kutner Bryan A. Simoni Jane M. Aunon Frances M. Creegan Emma Balán Ivan C. 《Archives of sexual behavior》2021,50(4):1651-1663
Archives of Sexual Behavior - Gay, bisexual, and other men who have sex with men (MSM) experience alarming HIV disparities alongside sub-optimal engagement in HIV interventions. Among MSM, stigma... 相似文献