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Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis.

Publication ,  Journal Article
Kimmerling, KA; Furman, BD; Mangiapani, DS; Moverman, MA; Sinclair, SM; Huebner, JL; Chilkoti, A; Kraus, VB; Setton, LA; Guilak, F; Olson, SA
Published in: Eur Cell Mater
January 31, 2015

Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.

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Published In

Eur Cell Mater

DOI

EISSN

1473-2262

Publication Date

January 31, 2015

Volume

29

Start / End Page

124 / 139

Location

United States

Related Subject Headings

  • X-Ray Microtomography
  • Wounds and Injuries
  • Tumor Necrosis Factor-alpha
  • Treatment Outcome
  • Time Factors
  • Temperature
  • Synovial Fluid
  • Peptides
  • Molecular Sequence Data
  • Mice, Inbred C57BL
 

Citation

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Kimmerling, K. A., Furman, B. D., Mangiapani, D. S., Moverman, M. A., Sinclair, S. M., Huebner, J. L., … Olson, S. A. (2015). Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. Eur Cell Mater, 29, 124–139. https://doi.org/10.22203/ecm.v029a10
Kimmerling, K. A., B. D. Furman, D. S. Mangiapani, M. A. Moverman, S. M. Sinclair, J. L. Huebner, A. Chilkoti, et al. “Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis.Eur Cell Mater 29 (January 31, 2015): 124–39. https://doi.org/10.22203/ecm.v029a10.
Kimmerling KA, Furman BD, Mangiapani DS, Moverman MA, Sinclair SM, Huebner JL, et al. Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. Eur Cell Mater. 2015 Jan 31;29:124–39.
Kimmerling, K. A., et al. “Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis.Eur Cell Mater, vol. 29, Jan. 2015, pp. 124–39. Pubmed, doi:10.22203/ecm.v029a10.
Kimmerling KA, Furman BD, Mangiapani DS, Moverman MA, Sinclair SM, Huebner JL, Chilkoti A, Kraus VB, Setton LA, Guilak F, Olson SA. Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. Eur Cell Mater. 2015 Jan 31;29:124–139.

Published In

Eur Cell Mater

DOI

EISSN

1473-2262

Publication Date

January 31, 2015

Volume

29

Start / End Page

124 / 139

Location

United States

Related Subject Headings

  • X-Ray Microtomography
  • Wounds and Injuries
  • Tumor Necrosis Factor-alpha
  • Treatment Outcome
  • Time Factors
  • Temperature
  • Synovial Fluid
  • Peptides
  • Molecular Sequence Data
  • Mice, Inbred C57BL