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Dive into the research topics where Heng Wu is active.

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Featured researches published by Heng Wu.


Nature Medicine | 2013

miR-214 targets ATF4 to inhibit bone formation

Xiaogang Wang; Baosheng Guo; Qi Li; Jiang Peng; Zhijun Yang; Aiyuan Wang; Dong Li; Zhibo Hou; Ke Lv; Guanghan Kan; Hongqing Cao; Heng Wu; Jinping Song; Xiaohua Pan; Qiao Sun; Shukuan Ling; Yuheng Li; Mu Zhu; Pengfei Zhang; Songlin Peng; Xiaoqing Xie; Tao Tang; An Hong; Zhaoxiang Bian; Yanqiang Bai; Aiping Lu; Yinghui Li; Fuchu He; Ge Zhang; Yingxian Li

Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.


Nature Medicine | 2012

A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy

Ge Zhang; Baosheng Guo; Heng Wu; Tao Tang; Bao-Ting Zhang; Lizhen Zheng; Yixin He; Zhijun Yang; Xiaohua Pan; Heelum Chow; Kinwah To; Yaping Li; Dahu Li; Xinluan Wang; Yi-Xiang J. Wang; Kwong-Man Lee; Zhibo Hou; Nan Dong; Gang Li; Kwok-Sui Leung; Leung-Kim Hung; Fuchu He; Lingqiang Zhang; Ling Qin

Metabolic skeletal disorders associated with impaired bone formation are a major clinical challenge. One approach to treat these defects is to silence bone-formation–inhibitory genes by small interference RNAs (siRNAs) in osteogenic-lineage cells that occupy the niche surrounding the bone-formation surfaces. We developed a targeting system involving dioleoyl trimethylammonium propane (DOTAP)-based cationic liposomes attached to six repetitive sequences of aspartate, serine, serine ((AspSerSer)6) for delivering siRNAs specifically to bone-formation surfaces. Using this system, we encapsulated an osteogenic siRNA that targets casein kinase-2 interacting protein-1 (encoded by Plekho1, also known as Plekho1). In vivo systemic delivery of Plekho1 siRNA in rats using our system resulted in the selective enrichment of the siRNAs in osteogenic cells and the subsequent depletion of Plekho1. A bioimaging analysis further showed that this approach markedly promoted bone formation, enhanced the bone micro-architecture and increased the bone mass in both healthy and osteoporotic rats. These results indicate (AspSerSer)6-liposome as a promising targeted delivery system for RNA interference–based bone anabolic therapy.


Nature Medicine | 2015

Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference–based bone anabolic strategy

Chao Liang; Baosheng Guo; Heng Wu; Ningsheng Shao; Defang Li; Jin Liu; Lei Dang; Cheng Wang; Hui Li; Shaohua Li; Wing Ki Lau; Yu Cao; Zhijun Yang; Cheng Lu; Xiaojuan He; Doris Wai-Ting Au; Xiaohua Pan; Bao-Ting Zhang; Changwei Lu; Hongqi Zhang; Kinman Yue; Airong Qian; Peng Shang; Jiake Xu; Lianbo Xiao; Zhaoxiang Bian; Weihong Tan; Zicai Liang; Fuchu He; Lingqiang Zhang

Currently, major concerns about the safety and efficacy of RNA interference (RNAi)-based bone anabolic strategies still exist because of the lack of direct osteoblast-specific delivery systems for osteogenic siRNAs. Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteoblasts, and then we developed CH6 aptamer–functionalized lipid nanoparticles (LNPs) encapsulating osteogenic pleckstrin homology domain-containing family O member 1 (Plekho1) siRNA (CH6-LNPs-siRNA). Our results showed that CH6 facilitated in vitro osteoblast-selective uptake of Plekho1 siRNA, mainly via macropinocytosis, and boosted in vivo osteoblast-specific Plekho1 gene silencing, which promoted bone formation, improved bone microarchitecture, increased bone mass and enhanced mechanical properties in both osteopenic and healthy rodents. These results indicate that osteoblast-specific aptamer-functionalized LNPs could act as a new RNAi-based bone anabolic strategy, advancing the targeted delivery selectivity of osteogenic siRNAs from the tissue level to the cellular level.


Biomaterials | 2015

A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts

Jin Liu; Lei Dang; Defang Li; Chao Liang; Xiaojuan He; Heng Wu; Airong Qian; Zhijun Yang; Doris W.T. Au; Michael W.L. Chiang; Bao-Ting Zhang; Quan-Bin Han; Kin Man Kevin Yue; Hong Qi Zhang; Changwei Lv; Xiaohua Pan; Jiake Xu; Zhaoxiang Bian; Peng Shang; Weihong Tan; Zicai Liang; Baosheng Guo; Aiping Lu; Ge Zhang

Dysregulated microRNAs in osteoclasts could cause many skeletal diseases. The therapeutic manipulation of these pathogenic microRNAs necessitates novel, efficient delivery systems to facilitate microRNAs modulators targeting osteoclasts with minimal off-target effects. Bone resorption surfaces characterized by highly crystallized hydroxyapatite are dominantly occupied by osteoclasts. Considering that the eight repeating sequences of aspartate (D-Asp8) could preferably bind to highly crystallized hydroxyapatite, we developed a targeting system by conjugating D-Asp8 peptide with liposome for delivering microRNA modulators specifically to bone resorption surfaces and subsequently encapsulated antagomir-148a (a microRNA modulator suppressing the osteoclastogenic miR-148a), i.e. (D-Asp8)-liposome-antagomir-148a. Our results demonstrated that D-Asp8 could facilitate the enrichment of antagomir-148a and the subsequent down-regulation of miR-148a in osteoclasts inxa0vivo, resulting in reduced bone resorption and attenuated deterioration of trabecular architecture in osteoporotic mice. Mechanistically, the osteoclast-targeted delivery depended on the interaction between bone resorption surfaces and D-Asp8. No detectable liver and kidney toxicity was found in mice after single/multiple dose(s) treatment of (D-Asp8)-liposome-antagomir-148a. These results indicated that (D-Asp8)-liposome as a promising osteoclast-targeting delivery system could facilitate clinical translation of microRNA modulators in treating those osteoclast-dysfunction-induced skeletal diseases.


Bone | 2014

Therapeutic RNA interference targeting CKIP-1 with a cross-species sequence to stimulate bone formation☆

Baosheng Guo; Bao-Ting Zhang; Lizhen Zheng; Tao Tang; Jin Liu; Heng Wu; Zhijun Yang; Songlin Peng; Xiaojuan He; Hongqi Zhang; Kevin K.M. Yue; Fuchu He; Lingqiang Zhang; Ling Qin; Zhaoxiang Bian; Weihong Tan; Zicai Liang; Aiping Lu; Ge Zhang

OBJECTIVESnCasein kinase 2 interacting protein 1 (CKIP-1) is a newly discovered intracellular negative regulator of bone formation without affecting bone resorption. In this study, we aimed to identify a cross-species siRNA sequence targeting CKIP-1 to facilitate developing a novel RNAi-based bone anabolic drug for reversing established osteoporosis.nnnMETHODSnEight specifically designed cross-species CKIP-1 siRNA sequences were screened in human, rhesus, rat and mouse osteoblast-like cells in vitro to identify the optimal sequence with the highest knockdown efficiency. The effect of this optimal siRNA sequence on osteogenic differentiation and matrix mineralization was further examined in osteoblast-like cells across different species, followed by an immunogenicity assessment in human peripheral blood mononuclear cells in vitro. The intra-osseous localization and silencing efficiency of the optimal siRNA were examined in vivo using a biophotonic system and real-time polymerase chain reaction, respectively. The RNAi-mediated cleavage of the CKIP-1 transcript was confirmed by rapid amplification of the 5 cDNA ends in vivo. Furthermore, the effect of the optimal siRNA sequence on osteogenic differentiation, bone turnover biomarkers, bone mass and micro-architecture parameters was investigated in healthy and osteoporotic rodents.nnnRESULTSnThe CKIP-1 siRNA sequence (si-3) was identified as the optimal sequence, which consistently maintained CKIP-1 mRNA/protein expression at the lowest level across species in vitro. The si-3 significantly increased mRNA expression levels of osteoblast phenotypic genes and matrix mineralization across species without inducing an immunostimulatory activity in vitro. The intra-osseous localization and RNAi-mediated CKIP-1 silencing with high efficiency were confirmed in vivo. Periodic intravenous injections of si-3 promoted mRNA expression of osteoblast phenotypic genes, enhanced bone formation, increased bone mass and elevated serum level of bone formation marker without raising urine level of bone resorption marker in the healthy rodents. Moreover, the si-3 treatment promoted bone formation, improved trabecular micro-architecture and reversed bone loss in the osteoporotic mice.nnnCONCLUSIONSnThe identified optimal CKIP-1 siRNA sequence (si-3) could promote osteogenic differentiation across species in vitro, stimulate bone formation in the healthy rodents and reverse bone loss in the osteoporotic mice.


Protocol exchange | 2014

Preparation of aptamer-functionalized lipid nanoparticles (LNPs) encapsulating siRNAs

Heng Wu; Chao Liang; Baosheng Guo; Lingqiang Zhang; Aiping Lu; Ge Zhang


Bone | 2010

A novel peptide for a drug delivery system to preferentially target bone formation sites

Heng Wu; Ge Zhang; Bao Sheng Guo; Tang Tao; Gang Li; Kwong Man Lee; Leung Kim Hung; Ling Qin


Archive | 2014

Development of aptamer-functionalized osteoblast-targeting lipid nanoparticles encapsulating osteogenic sirnas for bone anabolic therapy: Investigation of tisue-selective distribution, dose-response patern and persistence of gene silencing

Chao Liang; Baosheng Guo; Heng Wu; Lei Dang; Zhijun Yang; Liangqiang Zhang; Aiping Lu; Ge Zhang


Journal of orthopaedic translation | 2014

A novel bone targeting delivery system carrying bone-forming and anti-bone resorption phytomolecule icaritin for prevention of steroid-associated osteonecrosis in rat model

Shi Hui Chen; Xin Luan Wang; Li Zhen Zheng; Nan Wang; Jiayong Zhang; Heng Wu; Le Huang; Zhijun Yang; Ling Qin


Osteoporosis International | 2012

Aptamer facilitates osteogenic sirnas specifically targeting osteoblast and reducing their exporsure to hepatocyte in vivo

Chao Liang; Heng Wu; Baosheng Guo; Lei Zhang; Aiping Lu; Ge Zhang

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Ge Zhang

Hong Kong Baptist University

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Baosheng Guo

Hong Kong Baptist University

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Zhijun Yang

Hong Kong Baptist University

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Ling Qin

The Chinese University of Hong Kong

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Aiping Lu

Hong Kong Baptist University

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Tao Tang

The Chinese University of Hong Kong

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Chao Liang

Hong Kong Baptist University

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Gang Li

The Chinese University of Hong Kong

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Lingqiang Zhang

Dalian Medical University

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