Naringin-inlaid silk fibroin/hydroxyapatite scaffold enhances human umbilical cord-derived mesenchymal stem cell-based bone regeneration.
Zhao Zhi-Hu,Ma Xin-Long,Zhao Bin,Tian Peng,Ma Jian-Xiong,Kang Jia-Yu,Zhang Yang,Guo Yue,Sun Lei
Cell proliferation
OBJECTIVES:Large bone defects are a common, debilitating clinical condition that have substantial global health and economic burden. Bone tissue engineering technology has become one of the most promising approaches for regenerating defective bones. In this study, we fabricated a naringin-inlaid composite silk fibroin/hydroxyapatite (NG/SF/HAp) scaffold to repair bone defects. MATERIALS AND METHODS:The salt-leaching technology was used to fabricate the NG/SF/HAp scaffold. The cytocompatibility of the NG/SF/HAp scaffold was assessed using scanning electron microscopy, live/dead cell staining and phalloidin staining. The osteogenic and angiogenic properties were assessed in vitro and in vivo. RESULTS:The porous NG/SF/HAp scaffold had a well-designed biomimetic porous structure with osteoinductive and angiogenic activities. A gene microarray identified 854 differentially expressed genes between human umbilical cord-derived mesenchymal stem cells (hUCMSCs) cultured on SF-nHAp scaffolds and cells cultured on NG/SF/HAp scaffolds. The underlying osteoblastic mechanism was investigated using hUCMSCs in vitro. Naringin facilitated hUCMSC ingrowth into the SF/HAp scaffold and promoted osteogenic differentiation. The osteogenic and angiogenic capabilities of cells cultured in the NG/SF/HAp scaffold were superior to those of cells cultured in the SF/HAp scaffold. CONCLUSIONS:The data indicate the potential of the SF/HAp composite scaffold incorporating naringin for bone regeneration.
10.1111/cpr.13043
Naringin and bone marrow mesenchymal stem cells repair articular cartilage defects in rabbit knees through the transforming growth factor-β superfamily signaling pathway.
Ye Chao,Chen Jing,Qu Yi,Liu Hang,Yan Junxing,Lu Yingdong,Yang Zheng,Wang Fengxian,Li Pengyang
Experimental and therapeutic medicine
The present study aimed to assess the effect of a combination of naringin and rabbit bone marrow mesenchymal stem cells (BMSCs) on the repair of cartilage defects in rabbit knee joints and to assess possible involvement of the transforming growth factor-β (TGF-β) signaling pathway in this process. After establishing an articular cartilage defect model in rabbit knees, 20 New Zealand rabbits were divided into a sham operation group (Sham), a model group (Mod), a naringin treatment group (Nar), a BMSC group (BMSCs) and a naringin + BMSC group (Nar/BMSCs). At 12 weeks after treatment, the cartilage was evaluated using the International Cartilage Repair Society (ICRS)'s macroscopic evaluation of cartilage repair scale, the ICRS's visual histological assessment scale, the Modified O'Driscoll grading system, histological staining (hematoxylin and eosin staining, toluidine blue staining and safranin O staining) and immunohistochemical staining (type-II collagen, TGF-β3 and SOX-9 immunostaining). Using the above grading systems to quantify the extent of repair, histological quantification and macro quantification of joint tissue repair showed that the Nar/BMSCs group displayed repair after treatment in comparison to the untreated Mod group. Among the injury model groups (Mod, Nar, BMSCs and Nar/BMSCs), the Nar/BMSCs group displayed the highest degree of morphological repair. The results of histological and immunohistochemical staining of the repaired region of the joint defect indicated that the BMSCs had a satisfactory effect on the repair of the joint structure but had a poor effect on the repair of cartilage quality. The Nar/BMSCs group displayed satisfactory therapeutic effects on both repair of the joint structure and cartilage quality. The expression level of type-II collagen was high in the Nar/BMSCs group. Additionally, staining of TGF-β3 and SOX-9 in the Nar/BMSCs group was the strongest compared with that of any other group in the present study. Naringin and/BMSCs together demonstrated a more efficient repair effect on articular cartilage defects in rabbit knees than the use of either treatment alone in terms of joint structure and cartilage quality. One potential mechanism of naringin action may be through activation and continuous regulation of the TGF-β superfamily signaling pathway, which can promote BMSCs to differentiate into chondrocytes.
10.3892/etm.2020.9187
Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling.
Wang Wang,Mao Jie,Chen Yan,Zuo Jing,Chen Lin,Li Yajing,Gao Yingqian,Lu Qibin
Clinical and experimental pharmacology & physiology
Osteoporosis is a systemic bone metabolism disorder, which increases the risk of fractures, and in severe cases it may cause disability or even death. An important factor contributing to osteoporosis is the imbalance between bone formation and resorption. Naringin was reported to promote osteoblast differentiation, thus enhancing bone formation and alleviating osteoporosis development. However, the signalling pathways related to the regulatory mechanism of naringin in osteoporosis development are not clear. Proliferation of bone mesenchymal stem cells (BMSCs) treated with naringin in vitro was detected by CCK-8. An osteogenesis differentiation medium supplemented with naringin was applied to explore the effects of naringin on BMSC osteogenic differentiation, as detected by Alizarin red staining. Ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rats were orally administered with naringin. Dual-energy X-ray absorptiometry (DEXA) and micro-CT were applied to measure bone mineral density (BMD), bone volume/total volume (BV/TV), trabecula thickness (Tb.Th), trabecula number (Tb.N), trabecular separation (Tb.Sp) and bone surface/bone volume (BS/BV). H&E staining was performed to show pathological changes of the femur in PMOP rats after naringin treatment. Bone metabolism indicators were assessed by ELISA. We found that naringin suppressed the activation of the JAK2/STAT3 pathway. Naringin promoted BMSC proliferation and osteogenic differentiation. Furthermore, naringin alleviates bone loss and improves abnormal bone metabolism of PMOP rats. Collectively, naringin promotes BMSC osteogenic differentiation to ameliorate osteoporosis development by targeting JAK2/STAT3 signalling.
10.1111/1440-1681.13591
Electrosprayed naringin-loaded microsphere/SAIB hybrid depots enhance bone formation in a mouse calvarial defect model.
Yang Xue,Almassri Huthayfa N S,Zhang Qiongyue,Ma Yihui,Zhang Dan,Chen Mingsheng,Wu Xiaohong
Drug delivery
The burst release of active osteogenic factors, which is not beneficial to osteogenesis, is commonly encountered in bone tissue engineering. The aims of this study were to prepare naringin-loaded microsphere/sucrose acetate isobutyrate (Ng-m-SAIB) hybrid depots, reduce the burst release of naringin (Ng), and improve osteogenesis. The morphology and size distributions of electrosprayed Ng-microspheres were characterized by scanning electron microscopy (SEM). The Ng-microspheres and Ng-m-SAIB depots were characterized by Fourier transform infrared spectroscopy (FTIR) and in vitro release studies. In vitro osteoblast-microsphere interactions and in vivo osteogenesis were assessed after implantation of Ng-m-SAIB depots. The addition of sucrose acetate isobutyrate (SAIB) to monodisperse Ng-microspheres did not cause a change in the chemical structure. The performances of the microspheres in osteoblast-microsphere interactions were better when the naringin content was 4% than when it was at 2% and 6%. On the first day following the loading of Ng-microspheres (2%, 4%, and 6%) into SAIB depots, the burst release was reduced dramatically from 70.9% to 6.3%, 73.1% to 7.2%, and 73.9% to 9.9%, respectively. In addition, after 8 weeks, the new bone formation rate in the calvarial defects of SD rats receiving Ng-m-SAIB was 53.1% compared to 21.2% for the control group and 16.1% for the microsphere-SAIB group. These results demonstrated that Ng-m-SAIB hybrid depots may have promise in bone regeneration applications.
10.1080/10717544.2019.1568620
Effects of naringin on the proliferation and osteogenic differentiation of human amniotic fluid-derived stem cells.
Liu Meimei,Li Yan,Yang Shang-Tian
Journal of tissue engineering and regenerative medicine
Human amniotic fluid-derived stem cells (hAFSCs) are a novel cell source for generating osteogenic cells to treat bone diseases. Effective induction of osteogenic differentiation from hAFSCs is critical to fulfil their therapeutic potential. In this study, naringin, the main active compound of Rhizoma drynariae (a Chinese herbal medicine), was used to stimulate the proliferation and osteogenic differentiation of hAFSCs. The results showed that naringin enhanced the proliferation and alkaline phosphatase activity (ALP) of hAFSCs in a dose-dependent manner in the range 1-100 µg/ml, while an inhibition effect was observed at 200 µg/ml. Consistently, the calcium content also increased with naringin concentration up to 100 µg/ml. The enhanced osteogenic differentiation of hAFSCs by naringin was further confirmed by the dose-dependent upregulation of marker genes, including osteopontin (OPN) and Collagen I from RT-PCR analysis. The increased osteoprotegerin (OPG) expression and minimal expression of receptor activator of nuclear factor-κB ligand (RANKL) suggested that naringin also inhibited osteoclastogenesis of hAFSCs. In addition, the gene expressions of bone morphogenetic protein 4 (BMP4), runt-related transcription factor 2 (RUNX2), β-catenin and Cyclin D1 also increased significantly, indicating that naringin promotes the osteogenesis of hAFSCs via the BMP and Wnt-β-catenin signalling pathways. These results suggested that naringin can be used to upregulate the osteogenic differentiation of hAFSCs, which could provide an attractive and promising treatment for bone disorders. Copyright © 2014 John Wiley & Sons, Ltd.
10.1002/term.1911
[Effect of naringin combined with bone morphogenetic protein-2 on the proliferation and differentiation of MC3T3-E1 cells].
Gaoli Xu,Yi Liu,Lili Wu,Qiutao Shi,Guang Huo,Zhiyuan Gu
Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology
OBJECTIVE:This study evaluates the biological effects of naringin (NAR) joint bone morphogenetic protein (BMP)-2 on the proliferation, alkaline phosphatase (ALP) activity, and expression of osteoblastogenic genes, such as Runt-related transcription factor 2 (Runx2), collagen Ⅰ (ColⅠ), ALP, and osteocalcin (OCN) of pre-osteoblasts. METHODS:Three different NAR concentrations (10, 100, and 1 000 μmol·L⁻¹) were applied, alone or combined with BMP-2(50 ng·mL⁻¹), to restore the osteoblastogenesis of pre-osteoblasts (MC3T3-E1 cell line). Cell numbers (proliferation) were evaluated at first, fourth, and seventh days by Alamar blue assay. ALP activity and the expression of osteoblastogenic genes, such as Runx2, ColⅠ, ALP, and OCN were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) at fourth and seventh day. RESULTS:Stimulation by NAR alone and in combination with BMP-2 for 1 day and 4 days could promote cell proliferation, which peaked at a concentration of 100 μmol·L⁻¹ NAR combined with BMP-2 could promote cell proliferation significantly (P<0.05). Stimulation by NAR alone and in combination with BMP-2 for 4 and 7 days could promote ALP activity and bone-related gene(ALP, OCN, Runx2, ColⅠ) expression. ALP expression was significantly promoted after stimulation of 100 μmol·L⁻¹ NAR and BMP-2 (P<0.05). CONCLUSIONS:NAR exhibits promising potential for improving MC3T3-E1 proliferation and differentiation, and appropriate concentrations of NAR and BMP-2 show synergistic effect.
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10.7518/hxkq.2017.03.009