Table 2.
Summary of preclinical investigations on siRNAs-mediated targeting therapeutics in bone-related disorders.
| Disorders | Targeting gene | Delivery system | In vitro/In vivo | Outcome summary | Reference |
|---|---|---|---|---|---|
| Bone formation and resorption | FPPS | DharmaFECT4 (cationic lipid transfection reagent) | rat BMSC, MC3T3-E1 | Selectively inhibiting osteoclast-mediated bone resorption and improving osteoblast differentiation without effects on osteoblast mineralization | (Wang et al., 2011) |
| GNAS1, PHD2 | Ambion (polyamine-based transfection agent) | hBMSC, Sheep (local administration) | Both support bone regeneration in vivo, whereas only siGNAS1 promoted collagen I and osteopontin expression in vitro | (Ríos et al., 2012) | |
| siFlt-1, Ckip-1 | Lipofectamine 2000 complexes | rat BMSC, SD rat (local administration) | Satisfactory angiogenesis and osteogenesis in BMSCs and bone repair efficacy in vivo | (Jia et al., 2014) | |
| Ckip-1 | Lipofectamine 2000 complexes | MC3T3-E1,, C57/BL mice, SD rat (tail vein injection) | Increased osteogenic differentiation in vitro and reversed bone loss in osteoporotic mice | (Guo et al., 2014) | |
| Plekho1 | DOTAP cationic liposomes | SD rat (tail vein injection) | Increased bone microarchitecture and bone formation in both healthy and osteoporotic rats. | (Zhang et al., 2012a) | |
| Plekho1 | LNPs | SD rat (tail vein injection) | Improved bone mass in osteoporotic rats | (Liang et al., 2015) | |
| RANK | Cationic liposome DMAPAP/DOPE | C57BL/6 mice (local administration) | Effectively impeded osteolysis and increased bone formation | (Córdova et al., 2015) | |
| RANK | PLGA microparticles | mice BMSC | Inhibited osteoclastic phenotype | (Wang et al., 2012b) | |
| GCR | PLGA microparticles | hBMSC | Improved osteogenic proliferation and differentiation | (Hong et al., 2012) | |
| Sema4d | HPMA copolymer | Balb/c; Kunming mice (intravenous injection) | Partly counteracted bone loss originated from osteoporosis | (Zhang et al., 2014, Zhang et al., 2015b) | |
| Bone formation and resorption | Sema4d | PLLA scaffold | Wistar rat (local administration) | Improved bone formation in osteoporosis-related bone defects | (Zhang et al., 2016) |
| Noggin | PEG hydrogels scaffolds | hBMSC | Well guided osteogenic differentiation | (Nquyen et al., 2014) | |
| Noggin | PLA-DX-PEG | ICR mice (local administration) | Enhanced BMP-induced ectopic bone formation | (Manaka et al., 2011) | |
| Bone tumor | VEGF | Adenoviral vector | SaSO2 | Suppressed osteosarcoma angiogenesis and promoted apoptosis | (Peng et al., 2016) |
| VEGF | Adenoviral vector | SD rat (intratumoral injection) | Inhibited tumor growth | (Zhu and Mei, 2015) | |
| TCTP | Lentiviral particles | SaSO2, U2OS, MG63,nude mice (subcutaneous injection) | Promoted cell apoptosis and inhibited development of xenografts | (Shen et al., 2016) | |
| L1CAM | Liposome SN | PC3, nude mice (intratumoral injection) | Admirable suppression of PC proliferation and bone metastasis | (Sung et al., 2014) | |
| ABCB1 | Lipid-modified dextran polymer | KHOSR2, U2OSR2 | Reversed drug resistance of MDR cell lines | (Susa et al., 2010) | |
| ABCB1 | Lipofectant | hMNNG/HOS, 293T | Restored chemosensitivity in MDR cell lines | (Perez et al., 2011) | |
| VEGF | liposome-polycation-DNA (LPD) | NCI/ADR-RES,OVCAR-8, nude mice (tail vein injection) | Reversed MDR by multi-functional gene delivery systems | (Chen et al., 2010) | |
| CD147 | Adenoviral vector | Primary GCTB from patient | Dramatically inhibited proliferation, migration and invasion of GCTB cell | (Cheng et al., 2015) | |
| P63 | Lipofectamine RNAiMAX | Primary GCTSCs from patient | Dramatically inhibited proliferation of GCTB cell | (Lau et al., 2013) | |
| Bone tumor | EWS/FLI-1 | hydrogenated cationic nanodiamonds | A673 human; Ewing sarcoma cell line | Strongly inhibited oncogene expression and enhanced cytotoxic effect of vincristine | (Bertrand et al., 2015) |
| PI3Kcb | Adenoviral vector | MADB-106, SD rat (local administration) | Alleviated bone cancer pain (BCP) by increasing glia excitability | (Huang and Zhang, 2014) | |
| TLR4 | Adenoviral vector | Walker256, SD rat (intrathecal injection) | Attenuated nociception in rats with BCP | (Pan et al., 2015) | |
| PDGFR | HSV vector | SD rat (subarachnoid administration) | Effectively relieved BCPin the spinal cord | (Xu et al., 2016) | |
| CRTC1 | Adenoviral vector | NCTC2472, C3H/HeNCrl/Vr mice (intrathecal injection) | Reduced BCP in mice orthotopically implanted with OS cells | (Liang et al., 2016) | |
| SAON | Src | Lipofectamine 2000 complexes | New-Zealand white Rabbit (local administration) | Inhibited destructive repair of osteonecrosis | (Zheng et al., 2015, Cao et al., 2015a, Zheng et al., 2016) |
| PPAR-γ | Adenovirus shuttle vector | New-Zealand white Rabbit (local administration) | Inhibited adipogenesis of BMSCs and prevention of SAON in rabbit | (Li et al., 2014) | |
| MMP-13 | Dharmacon Accell | C57BL/6 mice (intra-articular injection) | Delayed cartilage degradation at the early stage of OA development | (Akagi et al., 2014) | |
| COL1A1, HtrA1 | Type I collagen sponges | Human articular chondrocyte (HAC), rabbit articular chondrocyte (RAC) | Enhanced differentiation index of chondrocytes cultured with BMP-2 under hypoxia condition | (Legendre et al., 2013, Ollitrault et al., 2015) | |
| ADAMTS-5 | Lentivirus vector | SD rat (intra-articular injection) | Protective effect on cartilage degradation | (Chu et al., 2013) | |
| HIF-2α | Chondrocyte- homing nanoparticles | Mouse (intra-articular injection) | Inhibited catabolic proteins expression in OA, and maintained cartilage integrity | (Pi et al., 2015) | |
| ADO2 | CLCN7 | Lipofectamine | RAW264.7, Human osteoclasts, mice (subcutaneous injection) | Inhibited increase of bone mass in growing ADO2 mice | (Capulli et al., 2015) |