Top-Down Fabricated microPlates for Prolonged, Intra-articular Matrix Metalloproteinase 13 siRNA Nanocarrier Delivery to Reduce Post-traumatic Osteoarthritis
Post-traumatic osteoarthritis (PTOA) associated with joint injury triggers a degenerative cycle of matrix destruction and inflammatory signaling, leading to pain and loss of function. Here, prolonged RNA interference (RNAi) of matrix metalloproteinase 13 (MMP13) is tested as a PTOA disease modifying therapy. MMP13 is upregulated in PTOA and degrades the key cartilage structural protein type II collagen. Short interfering RNA (siRNA) loaded nanoparticles (siNPs) were encapsulated in shape-defined poly(lactic-co-glycolic acid) (PLGA) based microPlates (μPLs) to formulate siNP-μPLs that maintained siNPs in the joint significantly longer than delivery of free siNPs. Treatment with siNP-μPLs against MMP13 (siMMP13-μPLs) in a mechanical load-induced mouse model of PTOA maintained potent (65-75%) MMP13 gene expression knockdown and reduced MMP13 protein production in joint tissues throughout a 28-day study. MMP13 silencing reduced PTOA articular cartilage degradation/fibrillation, meniscal deterioration, synovial hyperplasia, osteophytes, and pro-inflammatory gene expression, supporting the therapeutic potential of long-lasting siMMP13-μPL therapy for PTOA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
ACS nano - 15(2021), 9 vom: 28. Sept., Seite 14475-14491 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bedingfield, Sean K [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.10.2021 Date Revised 29.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acsnano.1c04005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Post-traumatic osteoarthritis (PTOA) associated with joint injury triggers a degenerative cycle of matrix destruction and inflammatory signaling, leading to pain and loss of function. Here, prolonged RNA interference (RNAi) of matrix metalloproteinase 13 (MMP13) is tested as a PTOA disease modifying therapy. MMP13 is upregulated in PTOA and degrades the key cartilage structural protein type II collagen. Short interfering RNA (siRNA) loaded nanoparticles (siNPs) were encapsulated in shape-defined poly(lactic-co-glycolic acid) (PLGA) based microPlates (μPLs) to formulate siNP-μPLs that maintained siNPs in the joint significantly longer than delivery of free siNPs. Treatment with siNP-μPLs against MMP13 (siMMP13-μPLs) in a mechanical load-induced mouse model of PTOA maintained potent (65-75%) MMP13 gene expression knockdown and reduced MMP13 protein production in joint tissues throughout a 28-day study. MMP13 silencing reduced PTOA articular cartilage degradation/fibrillation, meniscal deterioration, synovial hyperplasia, osteophytes, and pro-inflammatory gene expression, supporting the therapeutic potential of long-lasting siMMP13-μPL therapy for PTOA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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| 700 | 1 | |a Colazo, Juan M |e verfasserin |4 aut | |
| 700 | 1 | |a Di Francesco, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Danielle D |e verfasserin |4 aut | |
| 700 | 1 | |a Di Francesco, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Himmel, Lauren E |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Mukesh K |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Hongsik |e verfasserin |4 aut | |
| 700 | 1 | |a Hasty, Karen A |e verfasserin |4 aut | |
| 700 | 1 | |a Decuzzi, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Duvall, Craig L |e verfasserin |4 aut | |
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