CURRENT RESEARCH
Growth Plate Exhaustion and the Growth Plate Stem Cell
The rate of longitudinal bone growth (and hence linear growth of the
organism) falls progressively with age. In humans, fetal growth approaches
100 cm/year. At birth, the growth rate has decreased to 50 cm/year,
and by mid-childhood, 5 cm/year. A similar progressive decline in
bone growth occurs in other mammals. The differences among mammals
in final skeletal size (e.g. between a mouse and an elephant) appears
to be determined in part by the rapidity of this decline.
The decline in growth rate with increasing age is due largely to a decrease in the rate of growth plate chondrocyte proliferation. Growth plate transplantation experiments indicate that this decline in proliferation is not due to a hormonal or other systemic mechanism but rather to a mechanism intrinsic to the growth plate. We refer to this phenomenon as growth plate senescence.
Our findings suggest that growth plate senescence occurs
because the stem-like cells
in the resting zone
of the growth plate
have
a finite proliferative
potential. As the cells replicate, they gradually exhaust this potential,
causing growth to slow and finally come to a halt. Thus, growth plate
senescence appears not to be a function of time per se but rather
of the cumulative number of divisions that the stem-like cells have
undergone.
This concept, that growth plate senescence depends on cell replication, provides an explanation for the phenomenon of catch-up growth, the supranormal linear growth that occurs after release from growth-inhibiting conditions. This phenomenon was previously attributed to a central nervous system mechanism. However, the fact that growth inhibition also slows growth plate senescence suggests the following alternative explanation. The normal process of growth plate senescence depends on the cumulative number of replications that growth plate chondrocytes have undergone. Consequently, conditions that suppress growth plate chondrocyte proliferation conserve the proliferative capacity of the chondrocytes, thus slowing senescence. Therefore, following transient growth inhibition, growth plates retain a greater proliferative capacity, are less senescent, and hence show a greater growth rate than expected for age, resulting in catch-up growth. Our recent data suggest that this explanation applies also to human catch-up growth.
We are currently exploring the mechanisms that limit proliferation
of these stem-like cells.
|
