Signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes. RCGD423 is a small molecule gp130 modulator which can bias signalling towards anti-inflammatory and antidegenerative outputs. This small molecule increased proliferation while reducing apoptosis and hypertrophic responses in adult chondrocytes in vitro. In a rat partial meniscectomy model, RCGD423 greatly reduced chondrocyte hypertrophy, loss and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Furthermore, RCGD423 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[2]. Treatment of mice skin with 2 topical doses of RCGD423 (50uM) for 48h induced levels of both c-Myc and n-Myc as well as Ldha[3].
RCGD423 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Murine chondrocytes
5 μg/ml
24 hours
To evaluate the effect of RCGD423@MPDA on chondrocyte proliferation. Results showed that 5 μg/ml RCGD423@MPDA significantly increased the proportion of proliferating chondrocytes.
APL Bioeng. 2022 Apr 21;6(2):026101
RCGD423 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Osteoarthritis model
Intra-articular injection
20 μg/rat
Single injection, lasting 4 weeks
To evaluate the therapeutic effect of RCGD423@MPDA in an osteoarthritis model. Results showed that RCGD423@MPDA significantly reduced cartilage damage and proteoglycan loss, with better outcomes than RCGD423 or HA alone.
APL Bioeng. 2022 Apr 21;6(2):026101
Mice
Mouse hair cycle model
Topical administration
50uM
48 hours
RCGD423 binds to GP130, activating the Jak/Stat signaling pathway, inducing Myc and Ldha protein expression, increasing lactate dehydrogenase activity, and promoting hair follicle stem cell activation and hair cycle acceleration.
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