Small
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2023
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IF 13.3
Yongzhi Cui,Bin Lv,Zhongying Li,Chunming Ma,Zhengwei Gui,Yongtao Geng,Guohui Liu,Linchao Sang,Chen Xu,Qi Min,Li Kong,Zhiping Zhang,Yang Liu,Xiangbei Qi,Dehao Fu
Insufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis (PMOP). The existing drugs usually fail to re-establish the osteoblast/osteoclast balance from both sides and generate side-effects owing to the lack of bone-targeting ability. Here, engineered cell-membrane-coated nanogels PNG@mR&C capable of scavenging receptor activator of nuclear factor-κB ligand (RANKL) and responsively releasing therapeutic PTH 1–34 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane-coated chitosan biopolymers. The CXCR4 on the coated-membranes confer bone-targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1–34 triggered by osteoclast-mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone-specific accumulation. Thus, PNG@mR&C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re-establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.
研究领域:
生物医学工程
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药学
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组织工程
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骨生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2022
·
IF 4.014
Zhengtian Lyu,Haifang Li,Xin Li,Hui Wang,Hongchao Jiao,Xiaojuan Wang,Jingpeng Zhao,Hai Lin
ABSTRACT Fibroblast growth factor 23 ( FGF23 ), a bone-derived hormone, is involved in the reabsorption of phosphate ( P ) and the production of vitamin D hormones in the kidney. However, whether and how FGF23 regulates chicken bone metabolism remains largely unknown. In the present study, we investigated the effect of FGF23 on osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells ( BMSCs ). First, we found that the transcription of FGF23 was inhibited by β-glycerophosphate sodium ( GPS , 5 mM, 10 mM, 20 mM) and 10 −9 M 1, 25-dihydroxyvitamin D3 ( 1, 25(OH) 2 D 3 ), but was stimulated by 10 −7 M 1, 25(OH) 2 D 3 and parathyroid hormone ( PTH , 10 −9 M, 10 −8 M, 10 −7 M). Second, overexpression of FGF23 by the FGF23 adenovirus ( Adv-FGF23 ) suppressed the formation of mineralized nodules ( P < 0.001) and alkaline phosphatase ( ALP ) activity ( P < 0.05) in both differentiated and mineralized osteoblasts. Administration of FGF receptor 3 ( FGFR3 ) inhibitor (50 nM) was sufficient to restore the FGF23-decreased ALP activity ( P < 0.05), but not for the formation of mineralized nodules. In addition, the phosphorylation of ERK increased considerably with Adv-FGF23 overexpression ( P < 0.05). Administration of an ERK-specific inhibitor (10 μM) could down-regulate the phosphorylation of ERK ( P-ERK ) ( P < 0.05) and slightly restored the Adv-FGF23-reduction of ALP activity ( P = 0.08). In summary, our data suggest that GPS, 1, 25(OH) 2 D 3 , and PTH could regulate FGF23 mRNA expression in vitro. FGF23 is a negative regulator of bone remodeling. FGF23 not only inhibits BMSCs osteogenesis through the FGFR3-ERK signaling pathway but also suppresses the mineralization of mature osteoblasts.
研究领域:
骨生物学
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细胞生物学
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分子生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2023
·Vol. 12
·期 15
·2203099
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IF 10
Yanan Zhao,Honglei Kang,Xiaopei Wu,Pengzhen Zhuang,Rong Tu,Takashi Goto,Feng Li,Honglian Dai
Osteoporosis is a degenerative bone disease resulting from bone homeostasis imbalance regulated by osteoblasts and osteoclasts. Treating osteoporotic bone defects tends to be more difficult due to suppressed osteogenic differentiation, hyperactive osteoclastogenesis, and impaired angiogenesis. Hence, a drug carrier system composed of gelatin-coated hollow mesoporous silica nanoparticles (HMSNs/GM) loaded with pro-osteogenic parathyroid (PTH) and anti-osteoclastogenic alendronate (ALN) is constructed and compounded into calcium magnesium phosphate cement (MCPC). The spatial-temporal release of ions and drugs, controllable degradation rate, and abundant pore structure of MCPC composites enhance osteoporotic bone regeneration in ovariectomized rats by accelerating vascularization, promoting osteogenic differentiation and mineralization, and inhibiting osteoclastogenesis and bone resorption. The MCPC/HMSNs@ALN-PTH/GM demonstrates a synergistic threefold effect on osteogenesis, osteoclastogenesis, and angiogenesis. It improves the osteoporotic pathophysiological microenvironment and promotes osteoporotic vascularized bone defect regeneration, holding huge potential for other functional biomaterials design and clinical management.
研究领域:
生物材料科学
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组织工程
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骨科
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）