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Article ; Online: Focal adhesion kinase (FAK): its structure, characteristics, and signaling in skeletal system.

Huang, Yuping / Liao, Junguang / Vlashi, Rexhina / Chen, Guiqian

2023 Volume 111, Page(s) 110852

Abstract: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and distributes important regulatory functions in skeletal system. Mesenchymal stem cell (MSC) possesses significant migration and differentiation capacity, is an important source of ... ...

Abstract	Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and distributes important regulatory functions in skeletal system. Mesenchymal stem cell (MSC) possesses significant migration and differentiation capacity, is an important source of distinctive bone cells production and a prominent bone development pathway. MSC has a wide range of applications in tissue bioengineering and regenerative medicine, and is frequently employed for hematopoietic support, immunological regulation, and defect repair, although current research is insufficient. FAK has been identified to cross-link with many other keys signaling pathways in bone biology and is considered as a fundamental "crossroad" on the signal transduction pathway and a "node" in the signal network to mediate MSC lineage development in skeletal system. In this review, we summarized the structure, characteristics, cellular signaling, and the interactions of FAK with other signaling pathways in the skeletal system. The discovery of FAK and its mediated molecules will lead to a new knowledge of bone development and bone construction as well as considerable potential for therapeutic use in the treatment of bone-related disorders such as osteoporosis, osteoarthritis, and osteosarcoma.
Language	English
Publishing date	2023-08-14
Publishing country	England
Document type	Journal Article
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2023.110852
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Article ; Online: Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.

Vlashi, Rexhina / Zhang, Xingen / Li, Haibo / Chen, Guiqian

Reviews in endocrine & metabolic disorders

2023 Volume 25, Issue 2, Page(s) 339–367

Abstract: Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological ... ...

Abstract	Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.
MeSH term(s)	Humans ; Gene Editing/methods ; CRISPR-Cas Systems/genetics ; DNA
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-12-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2185718-0
ISSN	1573-2606 ; 1389-9155
ISSN (online)	1573-2606
ISSN	1389-9155
DOI	10.1007/s11154-023-09860-y
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Article ; Online: Correction to: Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.

Vlashi, Rexhina / Zhang, Xingen / Li, Haibo / Chen, Guiqian

Reviews in endocrine & metabolic disorders

2023 Volume 25, Issue 2, Page(s) 451–452

Language	English
Publishing date	2023-12-22
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	2185718-0
ISSN	1573-2606 ; 1389-9155
ISSN (online)	1573-2606
ISSN	1389-9155
DOI	10.1007/s11154-023-09867-5
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Article ; Online: Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.

Vlashi, Rexhina / Zhang, Xingen / Wu, Mengrui / Chen, Guiqian

Genes & diseases

2022 Volume 10, Issue 4, Page(s) 1291–1317

Abstract: Wnt signaling executes an indispensable performance in osteoblast differentiation, bone development, homeostasis, and remodeling. Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of β-catenin in the bone ... ...

Abstract	Wnt signaling executes an indispensable performance in osteoblast differentiation, bone development, homeostasis, and remodeling. Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of β-catenin in the bone environment. Going through the novel discoveries done via high-throughput sequencing technologies on genetic mouse models, we highlighted the significant contribution of Wnt ligands, co-receptors, inhibitors, their related skeletal phenotypes in mouse models and the similar bone disorders clinically observed in human beings. Moreover, the crosstalk between Wnt signaling pathway and BMP, TGF-β, FGF, Hippo, Hedgehog, Notch and PDGF signaling pathways is thoroughly demonstrated to be the underlying gene regulatory network that orchestrates osteoblast differentiation and bone development. We also introspected the significance of Wnt signaling transduction in the reorganization of cellular metabolism by stimulating glycolysis, glutamine catabolism, and fatty acid oxidation in osteoblast-lineage cells that display an important regulatory arbor in the cellular bioenergetics of the bone. Throughout this evaluation, most to date therapeutical approaches towards osteoporosis and other bone maladies found in human beings, are formulated with an aspiration to holistically revamp the present clinical applications involving various monoclonal antibodies therapies that lack specificity, efficacy, and safety into more requisite advanced therapeutics that satisfy these three requirements for further clinical considerations. Conclusively, our review provides comprehensive scientific findings related to the fundamental significance of Wnt signaling cascades in skeletal system and the underlying gene regulatory network with other signaling pathways enlightening researchers with the possibility to further integrate the identified target molecules into therapeutic strategies for skeletal disorders treatment in the clinic.
Language	English
Publishing date	2022-08-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2022.07.011
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Article ; Online: Ap-2β regulates cranial osteogenic potential via the activation of Wnt/β-catenin signaling pathway

Hu, Sujie / Chen, Sisi / Zeng, Haozu / Ruan, Xinyi / Lin, Xinyi / Vlashi, Rexhina / Zhou, Chenhe / Wang, Haidong / Chen, Guiqian

Developmental Biology. 2023 Sept., v. 501 p.81-91

2023

Abstract: The skull is a fundamental bone that protects the development of brain and consists of several bony elements, such as the frontal and parietal bones. Frontal bone exhibited superior in osteogenic potential and regeneration of cranial defects compared to ... ...

Abstract	The skull is a fundamental bone that protects the development of brain and consists of several bony elements, such as the frontal and parietal bones. Frontal bone exhibited superior in osteogenic potential and regeneration of cranial defects compared to parietal bone. However, how this regional difference is regulated remains largely unknown. In this study, we identified an Ap-2β transcriptional factor with a higher expression in frontal bone, but its molecular function in osteoblasts needs to be elucidated. We found that Ap-2β knockdown in preosteoblasts leads to reduced proliferation, increased cell death and impaired differentiation. Through RNA-seq analysis, we found that Ap-2β influences multiple signaling pathways including the Wnt pathway, and overexpression of Ap-2β showed increased nuclear β-catenin and its target genes expressions in osteoblasts. Pharmacological activation of Wnt/β-catenin signaling using LiCl treatment cannot rescue the reduced luciferase activities of the β-catenin/TCF/LEF reporter in Ap-2β knockdown preosteoblasts. Besides, transient expression of Ap-2β via the lentivirus system could sufficiently rescue the inferior osteogenic potential in parietal osteoblasts, while Ap-2β knockdown in frontal osteoblasts resulted in reduced osteoblast activity, reduced active β-catenin and target genes expressions. Taken together, our data demonstrated that Ap-2β modulates osteoblast proliferation and differentiation through the regulation of Wnt/β-catenin signaling pathway and plays an important role in regulating regional osteogenic potential in frontal and parietal bone.
Keywords	bone formation ; brain ; cell death ; luciferase ; osteoblasts ; sequence analysis ; skull ; transcription factors ; Osteoblast differentiation ; Ap-2β ; Wnt/β-catenin signaling ; Neural crest
Language	English
Dates of publication	2023-09
Size	p. 81-91.
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2023.06.015
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Article: The Antitumor Effect of Gene-Engineered Exosomes in the Treatment of Brain Metastasis of Breast Cancer.

Liu, Minchen / Hu, Yulan / Chen, Guiqian

Frontiers in oncology

2020 Volume 10, Page(s) 1453

Abstract: Strategies for treating brain metastases of breast cancer have demonstrated limited efficacy due to the blood-brain barrier (BBB). Gene therapy could improve the efficacy of chemotherapeutic drugs. Exosomes derived from the mesenchymal stem cells (MSCs) ... ...

Abstract	Strategies for treating brain metastases of breast cancer have demonstrated limited efficacy due to the blood-brain barrier (BBB). Gene therapy could improve the efficacy of chemotherapeutic drugs. Exosomes derived from the mesenchymal stem cells (MSCs) are small membrane-based gene vectors that can pass through the BBB. CXCR4 is the most commonly found chemokine receptor in human cancer cells. Furthermore, the SDF-1/CXCR4 axis plays an important role in the homing of MSCs for tumor cell diffusion and metastasis. TRAIL can selectively induce apoptosis in transformed cells without significant toxic side effects in normal tissues. In this study, exosomes were isolated from MSC
Language	English
Publishing date	2020-07-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.01453
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Article ; Online: Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies.

Juma, Salma Nassor / Liao, Junguang / Huang, Yuping / Vlashi, Rexhina / Wang, Qingwan / Wu, Bocong / Wang, Dan / Wu, Mengrui / Chen, Guiqian

Genes & diseases

2023 Volume 11, Issue 3, Page(s) 100986

Abstract: Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct ... ...

Abstract	Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs. This review summarized the osteoarthritis and psoriasis arthritis signaling pathways, crosstalk between BMP, WNT, TGF-β, VEGF, TLR, and FGF signaling pathways, biomarkers, and anatomical pathologies. Through bench research, we demonstrated that regenerative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses, multiple signaling blockers, and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation. Furthermore, we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.
Language	English
Publishing date	2023-06-19
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2023.04.021
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Article ; Online: Ap-2β regulates cranial osteogenic potential via the activation of Wnt/β-catenin signaling pathway.

Hu, Sujie / Chen, Sisi / Zeng, Haozu / Ruan, Xinyi / Lin, Xinyi / Vlashi, Rexhina / Zhou, Chenhe / Wang, Haidong / Chen, Guiqian

Developmental biology

2023 Volume 501, Page(s) 81–91

Abstract	The skull is a fundamental bone that protects the development of brain and consists of several bony elements, such as the frontal and parietal bones. Frontal bone exhibited superior in osteogenic potential and regeneration of cranial defects compared to parietal bone. However, how this regional difference is regulated remains largely unknown. In this study, we identified an Ap-2β transcriptional factor with a higher expression in frontal bone, but its molecular function in osteoblasts needs to be elucidated. We found that Ap-2β knockdown in preosteoblasts leads to reduced proliferation, increased cell death and impaired differentiation. Through RNA-seq analysis, we found that Ap-2β influences multiple signaling pathways including the Wnt pathway, and overexpression of Ap-2β showed increased nuclear β-catenin and its target genes expressions in osteoblasts. Pharmacological activation of Wnt/β-catenin signaling using LiCl treatment cannot rescue the reduced luciferase activities of the β-catenin/TCF/LEF reporter in Ap-2β knockdown preosteoblasts. Besides, transient expression of Ap-2β via the lentivirus system could sufficiently rescue the inferior osteogenic potential in parietal osteoblasts, while Ap-2β knockdown in frontal osteoblasts resulted in reduced osteoblast activity, reduced active β-catenin and target genes expressions. Taken together, our data demonstrated that Ap-2β modulates osteoblast proliferation and differentiation through the regulation of Wnt/β-catenin signaling pathway and plays an important role in regulating regional osteogenic potential in frontal and parietal bone.
MeSH term(s)	Wnt Signaling Pathway ; beta Catenin/metabolism ; Transcription Factors/metabolism ; Cell Differentiation ; Skull/metabolism ; Osteogenesis/physiology ; Osteoblasts ; Cells, Cultured
Chemical Substances	beta Catenin ; Transcription Factors
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2023.06.015
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Article ; Online: Regional difference in microRNA regulation in the skull vault.

Chen, Guiqian / Yao, Yifeng / Xu, Guangtao / Zhang, Xingen

Developmental dynamics : an official publication of the American Association of Anatomists

2019 Volume 248, Issue 10, Page(s) 1009–1019

Abstract: Background: The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest-derived frontal bone vs. mesoderm-derived parietal bone). Neural crest-derived frontal bone exhibits superior osteogenic activities and bone ... ...

Abstract	Background: The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest-derived frontal bone vs. mesoderm-derived parietal bone). Neural crest-derived frontal bone exhibits superior osteogenic activities and bone regeneration. MicroRNA (miRNA) has been emerged as a crucial regulator during organogenesis and is involved in a range of developmental processes. However, the underlying roles of miRNA regulation in frontal bone and parietal bone is unknown. Results: Total of 83 significantly expressed known miRNAs were identified in frontal bones versus parietal bones. The significantly enriched gene ontology and KEGG pathway that were predicted by the enrichment miRNAs were involved in several biological processes (cell differentiation, cell adhesion, and transcription), and multiple osteogenic pathways (e.g., focal adhesion, MAPK, VEGF, Wnt, and insulin signaling pathway. Focal adhesion and insulin signaling pathway were selected for target verification and functional analysis, and several genes were predicted to be targets genes by the differentially expressed miRNAs, and these targets genes were tested with significant expressions. Conclusions: Our results revealed a novel pattern of miRNAs in murine calvaria with dual tissue origins, and explorations of these miRNAs will be valuable for the translational studies to enhance osteogenic potential and bone regeneration in the clinic.
MeSH term(s)	Animals ; Bone Regeneration ; Focal Adhesions ; Frontal Bone/metabolism ; Insulin/metabolism ; Mice ; MicroRNAs/analysis ; MicroRNAs/physiology ; Osteogenesis ; Parietal Bone/metabolism ; Signal Transduction ; Skull/metabolism
Chemical Substances	Insulin ; MicroRNAs
Language	English
Publishing date	2019-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.97
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Article ; Online: HPVMD-C: a disease-based mutation database of human papillomavirus in China.

Yang, Zhenyu / Yi, Wenjing / Tao, Jin / Liu, Xiaoqing / Zhang, Michael Q / Chen, Guiqian / Dai, Qi

Database : the journal of biological databases and curation

2022 Volume 2022

Abstract: Human papillomavirus (HPV) can cause condyloma acuminatum and cervical cancer. Some mutations of these viruses are closely related to the persistent infection of cervical cancer and are ideal cancer vaccine targets. Several databases have been developed ... ...

Abstract	Human papillomavirus (HPV) can cause condyloma acuminatum and cervical cancer. Some mutations of these viruses are closely related to the persistent infection of cervical cancer and are ideal cancer vaccine targets. Several databases have been developed to collect HPV sequences, but no HPV mutation database has been published. This paper reports a Chinese HPV mutation database (HPVMD-C), which contains 149 HPV genotypes, 468 HPV mutations, 3409 protein sequences, 4727 domains and 236 epitopes. We analyzed the mutation distribution among HPV genotypes, domains and epitopes. We designed a visualization tool to display these mutations, domains and epitopes and provided more detailed information about the disease, region and related literature. We also proposed an HPV genotype prediction tool, which can predict HPV carcinogenic or non-carcinogenic risk genotypes. We expect that HPVMD-C will complement the existing database and provide valuable resources for HPV vaccine research and cervical cancer treatment. HPVMD-C is freely available at Database URL: http://bioinfo.zstu.edu.cn/hpv.
MeSH term(s)	Alphapapillomavirus/genetics ; Epitopes ; Female ; Genotype ; Humans ; Mutation ; Papillomaviridae/genetics ; Papillomavirus Infections/genetics ; Papillomavirus Infections/prevention & control ; Uterine Cervical Neoplasms/genetics
Chemical Substances	Epitopes
Language	English
Publishing date	2022-03-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/baac018
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