ESPE Yearbook of Paediatric Endocrinology

In Brief: Growth plate and articular cartilage have similar structures composed of distinct chondrocyte layers but they differ substantially with respect to their function and fate. This study combines transplantation experiments with cell tracing in rat with in vitrostudies to identify a novel mechanism by which synoviocytes act directly on chondrocytes to suppress endochondral and promote articular cartilage at the joint surface.

Commentary: Growth plate cartilage is responsible for elongation of the appendicular skeleton, whereas articular cartilage provides a low friction surface that protects the ends of long bones, despite their common origin from the early cartilage template. However, the key cellular and molecular mechanisms responsible for their divergent differentiation are unknown.

These authors investigated the role of the synovial microenvironment in the development of articular cartilage by transplanting osteochondral biopsies from distal femur intercondylar groove from donor rats and inserting them in distal femur in recipient rats, either with original orientation or inverted orientation placing the growth plate cartilage at the joint surface. Cells in the transplants could be traced using donor rats with ubiquitous expression of eGFP and eGFP-negative recipient rats. Interestingly, growth plate cartilage ectopically transplanted to the articular surface remodelled into articular-like cartilage with cells expressing Prg4 at the surface, whereas articular cartilage placed into the recipient growth plate was gradually remodelled into bone. These findings indicate that the synovial microenvironment acts directly on the articular cartilage to prevent endochondral bone formation and maintain the articular cartilage phenotype.

To further investigate this finding the authors used chondrocyte pellet cultures and showed that synoviocytes produce a soluble factor that directly prevents hypertrophic differentiation and promotes differentiation towards the articular phenotype.

This novel mechanism provides an answer to the long-standing question, why are the chondrocytes closest to the synovial joint space protected from endochondral bone formation and instead form articular cartilage. These findings have important implications for the understanding of skeletal development and joint formation, and also for the pathogenic mechanism of osteoarthritis and other degenerative joint diseases, as well as for tissue engineering of articular cartilage.