Figure 4. Alternative hypotheses to explain how resting chondrocytes acquire the ability to self-renew.

Hypothesis 1: As described by Newton et al., chondroprogenitor cells may undergo a radical switch at around 3 weeks of age to acquire self-renewal capacity and increased clonality. Hypothesis 2: There may be two distinct populations of chondroprogenitors, one that do not self-renew and get depleted in the first few weeks of life, after which the bone fide stem cells with self-renewal capacity get switched on. Hypothesis 3: Change of microenvironment (such as paracrine signal(s)) in the epiphysis results in a gradual transition of resting chondrocytes from favoring depletion to favoring self-renewal.