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Src blockage by siRNA inhibits VEGF-induced vascular hyperpemeability and osteoclast activity – an mechanism study for preventing destructive repair of osteonecrosis
Destructive repair is the pathological feature of ONFH characterized with the elevated vascular permeability and persistent bone resorption, which is associated with higher VEGF expression, activated c-Src, and vascular leakage. Activated c-Src also participates in mediating endothelial permeability and osteoclasts activity. However, the molecular mechanism of the VEGF and c-Src contributing to the destructive repair process remains unknown. The purpose of this study is to delineate the role of VEGF and c-Src in triggering destructive repair of osteonecrosis in vitro, as well as to elucidate if VEGF mediating vascular perm...
Source: Bone - December 29, 2014 Category: Orthopaedics Authors: Hui-Juan Cao, Li-Zhen Zheng, Nan Wang, Lin-Ying Wang, Ye Li, Dan Li, Yu-Xiao Lai, Xin-Luan Wang, Ling Qin Tags: Original Full Length Article Source Type: research

Anabolic Bone Formation Via a Site‐Specific Bone‐Targeting Delivery System by Interfering With Semaphorin 4d Expression
ABSTRACT Semaphorins have been recently targeted as new molecules directly implicated in the cell‐cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site‐specific bone‐targeting drug‐delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular u...
Source: Journal of Bone and Mineral Research - January 22, 2015 Category: Orthopaedics Authors: Yufeng Zhang, Lingfei Wei, Richard J Miron, Bin Shi, Zhuan Bian Tags: Original Article Source Type: research

Caspase-2 Modulates Osteoclastogenesis through Down-Regulating Oxidative Stress
In this study, we show that Casp-2 is involved in osteoclastogenesis. Protein levels of Casp-2 decrease during the differentiation of macrophages to osteoclasts. Furthermore, siRNA-mediated Casp-2 knockdown in osteoclast precursors or differentiation of bone marrow macrophage (BMM) precursors from Casp2-/- mice result in increased osteoclast numbers and tartrate-resistant acid phosphatase (TRAP) activity.
Source: Bone - March 19, 2015 Category: Orthopaedics Authors: Danielle A. Callaway, Manuel A. Riquelme, Ramaswamy Sharma, Marisa Lopez-Cruzan, Brian A. Herman, Jean X. Jiang Tags: Original Full Length Article Source Type: research

The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo
Conclusions GPRC6A, the likely receptor of osteocalcin (OC), is expressed in mouse muscle. ucOC treatment augments insulin-stimulated skeletal muscle glucose uptake in C2C12 myotubes and following ex vivo muscle contraction. ucOC may partly account for the insulin sensitizing effect of exercise.
Source: Osteoporosis International - August 10, 2015 Category: Orthopaedics Source Type: research

Expression of XBP1s in fibroblasts is critical for TiAl6V4 particle‐induced RANKL expression and osteolysis
This article is protected by copyright. All rights reserved
Source: Journal of Orthopaedic Research - September 25, 2015 Category: Orthopaedics Authors: Zhenheng Wang, Naicheng Liu, Gang Zhou, Tongguo Shi, Zhenzhen Wang, Jingjing Gan, Rui Wang, Hongbo Qian, Nirong Bao, Ting Guo, Jianning Zhao Tags: Research Article Source Type: research

CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function
The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs.
Source: Bone - November 7, 2015 Category: Orthopaedics Authors: Yuya Yoshioka, Mitsuaki Ono, Azusa Maeda, Tina M. Kilts, Emilio Satoshi Hara, Hany Khattab, Junji Ueda, Eriko Aoyama, Toshitaka Oohashi, Masaharu Takigawa, Marian F. Young, Takuo Kuboki Tags: Original Full Length Article Source Type: research

Clinical and biological significance of PIM1 kinase in osteosarcoma
This article is protected by copyright. All rights reserved
Source: Journal of Orthopaedic Research - December 19, 2015 Category: Orthopaedics Authors: Yunfei Liao, Yong Feng, Jacson Shen, Yan Gao, Gregory Cote, Edwin Choy, David Harmon, Henry Mankin, Francis Hornicek, Zhenfeng Duan Tags: Research Article Source Type: research

Heterozygous PTCH1 Mutations Impact the Bone Metabolism in Patients with Nevoid Basal Cell Carcinoma Syndrome Likely by Regulating SPARC Expression
This study sought to investigate the mechanism underlying heterozygous PTCH1 mutation‐mediated abnormal bone metabolism in patients with NBCCS. Stromal cells were isolated from the fibrous capsules of patients with NBCCS‐associated or non‐syndromic keratocystic odontogenic tumors and non‐syndromic tumor stromal cells without PTCH1 mutations served as controls. Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag‐labeled proteomics analysis. Our findings revealed that osteonectin/SPARC expression was significantly downreg...
Source: Journal of Bone and Mineral Research - February 17, 2016 Category: Orthopaedics Authors: Yingying Hong, Jianyun Zhang, Heyu Zhang, Xuefen Li, Jiafei Qu, Jiemei Zhai, Lei Zhang, Feng Chen, Tiejun Li Tags: Original Article Source Type: research

MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes
Conclusion Taken together, these results indicate that miR-20a may play a pivotal role in the NLRP3-inflammasome by targeted inhibit TXNIP expression in AA FLSs.
Source: Joint Bone Spine - February 29, 2016 Category: Orthopaedics Source Type: research

Small Players Ruling the Hard Game: siRNA in Bone Regeneration
Source: Journal of Bone and Mineral Research - May 16, 2016 Category: Orthopaedics Authors: Saber Ghadakzadeh, Mina Mekhail, Ahmed Aoude, Maryam Tabrizian, Reggie C Hamdy Tags: Erratum Source Type: research

Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways
Abstract Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increas...
Source: Calcified Tissue International - June 10, 2016 Category: Orthopaedics Source Type: research

Expression of XBP1s in fibroblasts is critical for TiAl6V4 particle ‐induced RANKL expression and osteolysis
This article is protected by copyright. All rights reserved
Source: Journal of Orthopaedic Research - September 24, 2015 Category: Orthopaedics Authors: Zhenheng Wang, Naicheng Liu, Gang Zhou, Tongguo Shi, Zhenzhen Wang, Jingjing Gan, Rui Wang, Hongbo Qian, Nirong Bao, Ting Guo, Jianning Zhao Tags: Research Article Source Type: research

SOD2 and Sirt3 Control Osteoclastogenesis by Regulating Mitochondrial ROS
This article is protected by copyright. All rights reserved
Source: Journal of Bone and Mineral Research - August 18, 2016 Category: Orthopaedics Authors: Haemin Kim, Yong Deok Lee, Hyung Joon Kim, Zang Hee Lee, Hong ‐Hee Kim Tags: Original Article Source Type: research

TET3 Mediates Alterations in the Epigenetic Marker 5hmC and Akt Pathway in Steroid ‐Associated Osteonecrosis
This article is protected by copyright. All rights reserved
Source: Journal of Bone and Mineral Research - August 31, 2016 Category: Orthopaedics Authors: Jie Zhao, Xin ‐long Ma, Jian‐xiong Ma, Lei Sun, Bin Lu, Ying Wang, Guo‐sheng Xing, Yan Wang, Ben‐chao Dong, Li‐yan Xu, Ming‐Jie Kuang, Lin Fu, Hao‐hao Bai, Yue Ma, Wei‐lin Jin Tags: Original Article Source Type: research

Osteogenic Potential of the Transcription Factor c-MYB
In conclusion, c-Myb plays a role in the osteogenesis of long bones by inducing osteogenic genes and causing the enhancement of mineral matrix production. This action of the transcription factor c-Myb might be of interest in the future for the establishment of novel approaches to tissue regeneration.
Source: Calcified Tissue International - December 23, 2016 Category: Orthopaedics Source Type: research

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