Chondrogenesis, bone morphogenetic protein-4 and mesenchymal stem cells

Abstract

Objective: As adult cartilage has very limited potential to regenerate, cartilage repair is challenging. Available treatments have several disadvantages, including formation of fibrocartilage instead of hyaline-like cartilage, as well as eventual ossification of the newly formed tissue. The focus of this review is the application of bone morphogenetic protein-4 (BMP-4) and mesenchymal stem cells (MSCs) in cartilage repair, a combination that could potentially lead to the formation of permanent hyaline-like cartilage in the defect.

Methods: This review is based on recent literature in the orthopaedic and tissue engineering fields, and is focused on MCSs and bone morphogenetic proteins (BMPs).

Results: BMP-4, a stimulator of chondrogenesis, both in vitro and in vivo, is a potential therapeutic agent for cartilage regeneration. BMP-4 delivery can improve the healing process of an articular cartilage defect by stimulating the synthesis of the cartilage matrix constituents: type II collagen and aggrecan. BMP-4 has also been shown to suppress chondrogenic hypertrophy and maintain regenerated cartilage. Use of an appropriate carrier for BMP-4 is crucial for successful reconstruction of cartilage defects. Due to the relatively short half-life in vivo of BMP-4, there is a need to localize and maintain the delivery of BMP-4 to the injury site. Additionally, the delivery of MSCs to the wound site could improve cartilage regeneration; therefore, the carrier should function both as a cell and a protein delivery vehicle.

Conclusion: The role of BMP-4 in chondrogenesis is significant, and successful methods to deliver BMP-4, with or without MSCs, to the cartilage defect site are a promising therapy to treat cartilage defects.