We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

LabMedica

Download Mobile App
Recent News Expo Clinical Chem. Molecular Diagnostics Hematology Immunology Microbiology Pathology Technology Industry Focus

Novel Drug Candidate Reverses Arthritic Bone Loss in Models

By LabMedica International staff writers
Posted on 21 Feb 2018
A small molecule drug candidate was found to induce bone regeneration and reduce inflammation in various rat osteoarthritis models.

Human adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in the development of osteoarthritis (OA), which is characterized by loss of bone matrix, hypertrophy, and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of pro-arthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself.

Image: Osteoarthritis leads to the progressive loss of joint cartilage, shown in red (Photo courtesy of Nancy Liu/Denis Evseenko Laboratory, University of Southern California).
Image: Osteoarthritis leads to the progressive loss of joint cartilage, shown in red (Photo courtesy of Nancy Liu/Denis Evseenko Laboratory, University of Southern California).

Investigators at the University of Southern California (Los Angeles, USA) sought potential drug candidates that would be able to reverse the inflammatory and degenerative effects of osteoarthritis while promoting regeneration and healing of bone and cartilage.

Towards this end, they used a high-throughput screening technique to identify a small molecule gp130 modulator from more than 170,000 candidate compounds. Gp130 is a transmembrane protein, which is the founding member of the class of all cytokine receptors. It forms one subunit of the type I cytokine receptor within the IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for signal transduction following cytokine engagement.

When tested on cultures of joint cartilage cells, the gp130 modulator, which was named RCGD 423 (regulator of cartilage growth and differentiation), caused increased cell proliferation and reduced the number of dying cells.

The investigators further reported in the February 2018 issue of the journal Annals of Rheumatic Diseases that in a rat partial meniscectomy model, RCGD 423 greatly reduced chondrocyte hypertrophy, loss, and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Moreover, RCGD 423 improved cartilage healing in a rat full-thickness osteochondral defect model, increasing proliferation of mesenchymal cells in the defect and also inhibiting breakdown of cartilage matrix in de novo generated cartilage.

"The goal is to make an injectable therapy for an early to moderate level of arthritis," said senior author Dr. Denis Evseenko, associate professor of orthopedic surgery at the University of Southern California. "It is not going to cure arthritis, but it will delay the progression of arthritis to the damaging stages when patients need joint replacements, which account for a million surgeries a year in the United States."

Related Links:
University of Southern California


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Specimen Collection & Transport
Complement 3 (C3) Test
GPP-100 C3 Kit
Gold Member
Real-time PCR System
GentierX3 Series

Latest BioResearch News

Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns

Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma

New Method Simplifies Preparation of Tumor Genomic DNA Libraries