Fig 5. Differences in bone length arise in part from modulation of the developmental program of growth plate senescence.

(A) Senescent changes in gene expression in the growth plate, including genes encoding many paracrine signaling molecules, are more advanced in the shorter bones. (B) Age-independent differences in gene expression within key regulatory pathways also contribute to differences in growth rate. (C) Consequently, the developmental program of growth plate senescence, including structural involution and declines in proliferation and hypertrophic cell size, is more advanced in shorter bones. (D) Differences in proliferation rate and hypertrophic cell size result in disparities in the rate of bone elongation and thus cumulative bone length. Bmp, bone morphogenetic protein; GP, growth plate; IGF, insulin-like growth factor; Igfbp, IGF-binding protein; Wif, Wnt inhibitory factor; Wnt, Wingless and Int-1.