A new study which explains the fundamental mechanism of how cartilage of the joints are formed during embryonic development, gives a clue to produce cartilage in the laboratory and opens up a new direction for treating the disease.
The laboratory produced cartilage may help replace cartilage damaged due to osteoarthritis.
During early embryonic development human limb skeleton comprises of only one element, completely made of cartilage. However, later these changes into a skeletal system composed of bone and lined by cartilage. The embryonic cartilage that develops into bones is called transient cartilage and the one that remains a cartilage is called permanent cartilage.
The research supported primarily by DBT’s Basic Research Division and published in the journal Development (15thMarch, 2015 issue), has explained how within the continuous cartilage element two distinct cell types, one of permanent cartilage and the other of transient cartilage are formed adjacent to each other.This is particularly important considering the fact that during the onset of osteoarthritis the permanent cartilage starts to behave like transient cartilage.
The study carried out by scientists of Biological Sciences and Bioengineering department of IIT Kanpur showed that all newly formed cartilage cells are bi-potential and are thus capable of differentiating into transient as well as permanent cartilage. However, a difference in the cell signals leads to major part of it growing into transient cartilage, ultimately developing into bones and the part adjoining the forming joint remains cartilage.
BMP is a pro-transient cartilage signal and Wnt is a pro-permanent cartilage signal. When the site of segmentation of the limb becomes distinct, a BMP inhibitor (Noggin) mRNA is expressed in a wide area within the developing cartilage, other than in the cells at the joints (interzone).
During this early cartilage development, BMP signaling is restricted to the periphery of the forming cartilage. As development progresses, the BMP inhibitor’s (Noggin)area of play becomes restricted within bands near the ends of the forming skeletal elements, a few cell layers away from the interzone. As a result, the BMP signaling domain expands but the cells on either side of forming joints remain insulated.
Wnt ligands that are produced at the joints (interzone) signal the cells around the joints to promote permanent cartilage fate. At later developmental stages, this promotion is further consolidated. The progeny of the proliferative bi-potentialcartilage (cells with potential to form either transient or permanent cartilage) cells that expand towards the interzone turn off transient cartilage differentiation capability but retain their cartilage characteristics.
These cartilage cells, sandwiched between the BMP and Wnt signaling domains, are capable of undergoing transient as well as articular cartilage differentiation i.e. retain their bi-potential nature. When these cells come under the influence of Wnt signaling, they differentiate as articular cartilage. On the other hand, the progeny of the proliferative bi-potentialcartilage cells that expand towards the future bone region come within the zone of BMP signaling influence and differentiate as transient cartilage.
With the rules that govern the differentiation of permanent and transient cartilage elucidated, it could help regenerative as well as pharmacological treatment of osteoarthritis.
Scientist teams at some of the autonomous institutes like the National Centre for Cell Sciences at Pune are also working on various aspects of osteoarthritis.