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bone morphogenic protein signaling in spinal cord injury

Neuroimmunology and Neuroinflammation 2021年第1期8卷 53-63页

作者： Nadia Al-Sammarraie Swapan K.Ray Department of Pathology Microbiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSC 29209USA

Spinal cord injury(SCI)is a debilitating injury that results from traumatic or non-traumatic insults to the spinal cord,causing significant impairment of the patient's activity and quality of *** morphogenic proteins(BMPs)are a group of polyfunctional cytokines belonging to the transforming growth factor beta superfamily that regulates a wide variety of cellular functions in healthy and disease *** studies suggest that dysregulation of BMP signaling is involved in neuronal demyelination and death after traumatic *** focus of this article is to describe our current understanding of the role of BMP signaling in the regulation of cell fate,proliferation,apoptosis,autophagy,and inflammation in traumatic ***,we will describe the expression of BMPs and pattern of BMP signaling before and after traumatic SCI in rodent models and in ***,we will discuss the role of BMP in the regulation of neuronal and glial cell differentiation,survival,functional recovery from traumatic SCI,and the gap in knowledge in this area that requires further investigation to improve SCI prognosis.

关键词： Spinal cord injury bone morphogenic protein apoptosis proliferation autophagy differentiation inflammation

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Model-based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in bone

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Genomics, Proteomics & Bioinformatics 2007年第3期5卷 158-165页

作者： Andy B. Chen Kazunori Hamamura Guohua Wang Weirong Xing Subburaman Mohan Hiroki Yokota Yunlong Liu Departments of Biomedical Engineering/Anatomy and Cell Biology Indiana University-Purdue University Indianapolis Indianapolis IN 45202 USA Division of Biostatistics Department of Medicine Center for Computational Biology and Bioinformatics Indiana University School of Medicine Indianapolis IN 46202 USA School of Computer Science and Technology Harbin Institute of Technology Harbin 150001 China Musculoskeletal Disease Center JP Pettis Memorial Veterans Administration Medical Center Loma Linda CA 92357 USA

Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs （TFBMs） through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins （BMPs） are two known treatments to strengthen bone. We addressed a question： Is there any TFBM that stimulates both ＂anabolic responses of mechanical loading＂ and ＂BMP-mediated osteogenic signaling＂？ Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor （PPAR）. The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.

关键词： microarray transcription-factor binding motif mechanical loading bone morphogenic protein ant algorithm

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Tissue engineering in mandibular reconstruction: osteogenesis-inducing scaffolds

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Plastic and Aesthetic Research 2019年第9期6卷 1-12页

作者： Laurel Nelms William Jack Palmer University of California Riverside School of Medicine RiversideCA 92521USA Boston University School of Medicine BostonMA 02118USA.

Currently, the gold standard for aesthetic and functional reconstruction of critical mandibular defects is an autologous fibular flap;however, this carries risk of donor site morbidity, and is not a promising option in patients with depleted donor sites due to previous surgeries. Tissue engineering presents a potential solution in the design of a biomimetic scaffold that must be osteoconductive, osteoinductive, and support osseointegration. These osteogenesis-inducing scaffolds are most successful when they mimic and interact with the surrounding native macro- and micro-environment of the mandible. This is accomplished via the regeneration triad: (1) a biomimetic, bioactive osteointegrative scaffold, most likely a resorbable composite of collagen or a synthetic polymer with collagen-like properties combined with beta-tri calcium phosphate that is 3D printed according to defect morphology;(2) growth factor, most frequently bone morphogenic protein 2 (BMP-2);and (3) stem cells, most commonly bone marrow mesenchymal stem cells. Novel techniques for scaffold modification include the use of nano-hydroxyapatite, or combining a vector with a biomaterial to create a gene activated matrix that produces proteins of interest (typically BMP-2) to support osteogenesis. Here, we review the current literature in tissue engineering in order to discuss the success of varying use and combinations of scaffolding materials (i.e., ceramics, biological polymers, and synthetic polymers) with stem cells and growth factors, and will examine their success in vitro and in vivo to induce and guide osteogenesis in mandibular defects.

关键词： Osteogenic scaffolds mandibular reconstruction tissue engineering regeneration triad bone morphogenic protein bone marrow mesenchymal stem cells beta-tri calcium phosphate gene activated matrix

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KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells

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International Journal of Oral Science 2013年第4期5卷 200-205页

作者： Juan Xu Bo Yu Christine Hong Cun-Yu Wang Department of Stomatology Chinese People's Liberation Army General Hospital Division of Oral Biology and Medicine School of DentistryUniversity of California Section of Orthodontics School of DentistryUniversity of California Department of Bioengineering Henry Samueli School of Engineering and Applied ScienceUniversity of California

Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.

关键词： bone morphogenic protein dental mesenchymal stem cell epigenetics KDM6B odontogenic differentiation

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