Implications of siRNA Therapy in Bone Health: Silencing Communicates
Abstract
:1. Introduction
2. Methodology
3. Therapeutic Interventions of siRNA in Major Bone Disorders
3.1. Small Interfering RNA Therapy for Osteoporosis
3.2. Small Interfering RNA Therapy for Osteoarthritis
3.3. Small Interfering RNA Therapy for Rheumatoid Arthritis
3.4. Small Interfering RNA Therapy for Intervertebral Degenerative Disc Disease
3.5. Small Interfering RNA Therapy for Fracture Healing
4. Mechanisms for siRNA Delivery in Bone Disorders
4.1. Cationic Polymer-Based Delivery Systems
4.1.1. Cationic Polymer-Derived Nanoparticles
4.1.2. Spermine-Based Delivery System
4.1.3. Chitosan-Mediated Delivery System
4.1.4. Atelocollagen-Mediated Delivery System
4.1.5. Albumin-Based Nanoparticles
S.No. | Delivery Method | Target | MAIN OUTCOME | Species/Model/Tissue Type | Reference |
---|---|---|---|---|---|
1. | Cationic Polymer-derived nanoparticles (Ac-PLGA-PEI) | MMP-2 | Effective silencing of MMP-2 expression, which prevented chondrocyte dedifferentiation. | Human/in vitro/PC3 and C20A4 cell lines of prostate cancer and chondrocytes, respectively. | [66] |
2. | Spermine-based polyplexes (PSI) | Chordin | Knockdown of the Chordin gene, which induced osteoblast differentiation and bone regeneration. | Human/in vitro/bone-forming MSCs of nonunion fracture patients. Mouse/in vivo/tibial monocortical defect model. | [59] |
3. | Chitosan-mediated delivery method (FA-coupled PLLD and azidized chitosan) | AEG-1 | Efficient inhibition of AEG-1 expression provoked anti-invasive effects. | Human/in vitro/143B, and U20S cell lines of osteosarcoma. Mouse/in vivo/143B cell-inoculated nude athymic model. | [71] |
4. | Atelocollagen-based delivery system | EZH-2 and p100-α | Knockdown of EZH2 and P100-α genes causes suppression of bone tumors without eliciting an auto-immune response. | Human/in vitro/PC-3M-luc-C6 prostate cancer cell line. Mouse/in vivo/PC-3M-luc-C6 in a nude athymic model. | [73] |
5. | Albumin-derived nanodroplets (ultrasound-driven) | CTSK | Repression of CTSK expression, which prompted the inhibition of osteoclastogenesis. | Human/in vitro/MSCs and osteoclast precursors. | [28] |
6. | Nanomicelles (LA combined with the cross-linked peptide LACL) | SBREP1 | Efficient silencing of the SBREP1 gene evoked anti-metastatic conditions. | Human/in vitro/PC-3 and C4-2B cell lines of BmCRPC. Mouse/in vivo/BALB/c model. | [75] |
7. | Liposomes (Lipofectamine RNAiMAX) | mTORC1, C2, RICTOR and RAPTOR | Suppression of respective genes, which promoted ECM formation and halted apoptosis and senescence. | Human/in vitro/disc NP cells derived from IVDD patients who have undergone lumbar interbody fusion surgery. | [76] |
8. | Solid lipid nanoparticles (PEGylated) | TNF-α | Decrease in inflammation and joint healing as a result of knockdown of TNF-α gene expression. | Mouse/in vitro and in vivo/J774A.1 macrophage cell line, LPS-induced inflammation, and collagen-induced arthritis model. | [77] |
9. | Exosomes (conjugated with bone targeting peptide) | Shn3 | Shn3 gene silencing led to upregulation of osteogenesis and increased vascularization. | Mouse/in vitro and in vivo/Raw264.7 and MC3T3-E1 cell lines of macrophages and osteoblast precursors, respectively. | [78] |
10. | Titanium Implants (coated with nanoparticle film) | Ckip-1 | Effective inhibition of Ckip-1 expression augmented ECM mineralization and osteoblast differentiation. | Human/in vitro/H1299 and MG63 cell lines of lung carcinoma and osteosarcoma, respectively. | [79] |
11. | Iron Oxide nanocages (magnetic field directed) | mGluR5 | Decline in mGluR5 gene expression reduced anti-proliferative effects. | Human/in vitro/LM7 cell line of osteosarcoma. Mouse/in vitro/OS482 cell line of osteosarcoma. | [80] |
12. | Cerium Oxide nanobubbles | CTSK | Silencing of CTSK expression elevated osteogenesis and suppressed osteoclastogenesis. | Human/in vitro/MSCs and osteoclast precursors. | [30] |
13. | MBG nanospheres | RANK | Blocking of NF-kB signaling causes repression of osteoclastogenesis. | Mouse/in vitro/Raw264.7 macrophage cell line and osteoclast precursors. | [24] |
14. | DSS-6 oligopeptide nanocarriers (complexed with cationic liposomes) | CrkII | Increased bone mass results from effective knockdown of the CrkII gene. | Mouse/in vivo/RANKL-induced bone loss model. | [29] |
15. | (Asp) 8 oligopeptide nanoparticles (complexed with HPMA) | sema4D | Reduced expression of sema4D stimulates bone surface remodeling and recovery from bone loss. | Mouse/in vitro/BMSCs and BMMs from the Kunming mouse model. Mouse/in vivo/OVX osteoporotic mouse model. | [81] |
16. | Aptamer based nanoparticles | BMP-2 | Downregulation of the TNF-α-dependent NF-kB pathway led to the healing of joints and a decrease in edema. | Human/in vitro/MSCs. Mouse/in vivo/curdlan-treated Zap70mut ankylosing spondylitis model. | [82] |
17. | Nucleofection (kit with reagents) | PI3Kδ | Repression of PDGF-dependent Rac-1 activation enhanced anti-arthritic effects. | Human/in vitro/FLS cells from OA and RA patients who underwent synovectomy. | [83] |
18. | OC/GCA-cross-linked hydrogel | p65 | Protection from disc degeneration as a consequence of suppression of NF-kB-mediated NLRP3 inflammasome activation. | Human/in vitro/disc NP cells. Rat/in vivo/NP cells of the IVDD model. | [52] |
19. | CdTe/ZnS/3-MPA QDs (combined with β-CD and CKKRGD) | PPARγ | Decrease in PPARγ expression led to an enhancement of osteogenesis. | Human/in vitro/MSCs. Mice/in vivo/hMSCs implanted a nude athymic model. | [84] |
20. | Carbon Dots (bioconjugated with sulfo-SMCC) | TNF-α | Suppression of TNF-α-directed pathways, elevated chondrogenesis, and cartilage regeneration in the patellar joint | Rat/in vitro/MSCs from the femur and tibia. Rat/in vivo/MSCs implanted in SD patellar joint defect model. | [85] |
4.2. Lipid-Based Delivery Systems
4.2.1. Nanomicelles-Based Delivery System
4.2.2. Liposomes-Based Delivery Systems
4.3. Aptamer-Based Delivery System
4.4. Inorganic-Based Delivery Systems
4.4.1. Titanium Implant-Based Delivery System
4.4.2. Iron Oxide Nanocage-Based System
4.4.3. Cerium Oxide Nanoparticles
4.4.4. Silica-Based Nanoparticles
4.5. Nucleofection-Based Delivery System
4.6. Quantum Dot-Based Delivery System
4.7. Hydrogel-Based Delivery System
5. A Combinatorial Approach to siRNA Therapy for Various Bone Disorders
6. Clinical Implications and Future Strategies
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Singh, P.; Singh, M.; Singh, B.; Sharma, K.; Kumar, N.; Singh, D.; Klair, H.S.; Mastana, S. Implications of siRNA Therapy in Bone Health: Silencing Communicates. Biomedicines 2024, 12, 90. https://doi.org/10.3390/biomedicines12010090
Singh P, Singh M, Singh B, Sharma K, Kumar N, Singh D, Klair HS, Mastana S. Implications of siRNA Therapy in Bone Health: Silencing Communicates. Biomedicines. 2024; 12(1):90. https://doi.org/10.3390/biomedicines12010090
Chicago/Turabian StyleSingh, Puneetpal, Monica Singh, Baani Singh, Kirti Sharma, Nitin Kumar, Deepinder Singh, Harpal Singh Klair, and Sarabjit Mastana. 2024. "Implications of siRNA Therapy in Bone Health: Silencing Communicates" Biomedicines 12, no. 1: 90. https://doi.org/10.3390/biomedicines12010090