A biography of the chondrocyte

Significant gaps persist in our understanding of chondrocyte biology. We do not know when, how, or even whether these cells are replenished throughout the normal, human life span. We are taught that as much as 90% of the cartilage is "metabolically inert" interterritorial matrix, but we do not know how this substance is regularly replaced (as it is known to be) by the distant chondrocytes, We recognise that the "tidemark" is the most conspicuous histological feature within cartilage, but we do not understand why that layer stains with haematoxylin or what that may imply for the biology of the tissue. These, and other issues may be clarified if the lifetime of each chondrocyte begins as a mesenchymal stem cell at the articular margin, plays out over years on an arcing trajectory along collagenous guidelines, and ends as an extracellular deposit of intracellular remains at the interface between uncalcified and calcified cartilage. This hypothesis is presented here, and some of its potential implications are considered.