Teneurin-4, a transmembrane protein, is a novel regulator that suppresses chondrogenic differentiation.

“Teneurin-4 (Ten-4), a transmembrane protein, is expressed in the nervous systems and the mesenchymal tissues, including the cartilage.  Ten-4 was highly expressed in the mesenchymal condensation area of the mouse femur at embryonic day (E) 13.5, while its expression was decreased in the growth plate of the femur at E18.5{So Ten-4 could be vital in the initial growth plate formation}. Using the cartilage-like pellet culture of human synovial mesenchymal cells, Ten-4 expression was induced and peaked 7 days after induction of differentiation, while a production of type II and X collagens was increased after Day 14. In the cartilage-like pellet, Ten-4 was highly expressed in the less differentiated region. In the chondrogenic cell line ATDC5, knockdown of Ten-4 expression significantly increased the alcian blue staining and expression levels of aggrecan and type II and X collagens. Further, an elevated expression of Sox6, Sox9, and Runx2 and an attenuation of the ERK activation were observed in the Ten-4-knockdown ATDC5 cells{Well ATDC5 cells are already pre-chondrogenic}.”

In the adult body we are dealing with mesenchymal stem cells rather than pre-chondrogenic cells like ATDC5 cells or cells in the zone of ranvier.  If Ten4 is responsible for initial mesenchymal condensation that is more important than any adverse affects later.

“. Inhibition and promotion of ERK activation increases and decreases proteoglycan synthesis, respectively, in human chondrocytes and the mouse chondrogenic cell line ATDC5, indicating that the ERK signaling negatively regulates chondrocyte differentiation.”<-LSJL increases ERK signaling and ERK signaling may be the start of that initial growth plate formation even if it’s detrimental later.

“Ten-3 is expressed in the cartilage tissues during mouse development. Ten-3 expression is observed in the fibrous layer of the mandibular condylar cartilage, the perichondrium of the growth plate cartilage, and proliferative chondrocytes of the both cartilage tissues, but not in hypertrophic chondrocytes.”

“The high expression of Ten-4 is observed in the mesenchymal condensation area”