Extracellular matrix protection factor 1 (ECPF-1), a novel osteoarthritis therapeutic demonstrates chondroprotective properties in a rat model of osteoarthritis; a microcomputed tomography and histological analysis

Amy Bhatt, Brian Heist, Joseph Musiol, Jamil Shariff, Jazmine Loman, Paige Black, Frederick J Lombard, Ellen Cho, Sarah Chmielewski, Tiffany C Holmes, Belinda Beqo, Jeremiah Kinsey, Patrisia Mattioli, Lyudamila Lukashova, Abdulhafez A Selim, Marina D'Angelo

Research output: Contribution to conferencePresentation

Abstract

Introduction: Osteoarthritis (OA) is a common degenerative joint disease of multifactorial etiology causing pain and disability in more than 25% of the adult population. Despite affecting a vast amount of the population, there is currently no therapy available that successfully suspends or reverses the deterioration of cartilage and bone occurring in OA.

Objectives: Current pharmacological treatment of OA targets inflammation and pain management through non-steroidal anti-inflammatory drugs, intra-articular corticosteroids, and analgesics. Extracellular Matrix Protection Factor 1 (ECPF-1) is a novel therapeutic that inhibits specific matrix metalloproteinases (MMPs) that are involved in degradation of the extracellular matrix (ECM) in cartilage during OA.

Methods: In this study, a chemically-induced rat model of OA in the knee joint was utilized to investigate the effects of ECPF-1 at various concentrations in early stage osteoarthritis. The progression of post-traumatic OA in this study was assessed using microcomputed tomography (µCT) and histological analysis via Hematoxylin and Eosin, Safranin-O, and Periodic acid–Schiff staining. The acute effects of OA progression were studied on a timeline of 4 and 8 weeks.

Results: The µCT data showed that at both the 4-week post-loading (4 weekly injections of ECPF-1) and 8-week protection-extension phases, the ECPF-1 treated cohort demonstrated decreased ECM degradation compared to untreated controls. Improved articular cartilage histological staining of the ECPF-1 treated joints supported the µCT image data for the femur and tibia.

Discussion: These results show that ECPF-1 could be utilized in chondroprotection against alteration of ECM metabolism involved in OA. This study shows a potential for ECPF-1 as a possible therapeutic for slowing the progression of OA in an acute setting.

Original languageAmerican English
StatePublished - May 10 2021

Keywords

  • Safranin stain
  • microcomputed tomography
  • osteoarthritis treatment

Disciplines

  • Life Sciences
  • Medicine and Health Sciences

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