Differential ageing of growth plate cartilage determines skeletal proportions

Bones at different anatomical locations vary dramatically in size. The mechanisms responsible for these size differences are poorly understood. Bone elongation occurs at the growth plates and advances rapidly in early life but then progressively slows due to a developmental program termed growth plate senescence. This developmental program includes declines in cell proliferation and hypertrophy, depletion of cells in all growth plate zones, and extensive underlying changes in the expression of growth-regulating genes. Here we use RNA-Seq to compare changes of gene expression with age in the longer bone (tibia, 1- vs 4-wk) with the difference of gene expression between long and short bones (tibia vs phalanx) at 1wk. We found that the developmental program of growth plate senescence is more advanced in the shorter bone and this differential senescence (or aging) underlies the disparities in bone length.

不同解剖部位的骨骼尺寸差异悬殊，而造成此类尺寸差异的分子机制目前仍知之甚少。骨骼的伸长发生于生长板（growth plate），在生命早期快速进行，但随后会因一种被称为生长板衰老的发育程序而逐渐放缓。该发育程序涵盖细胞增殖与肥大能力的下降、所有生长板区域细胞的耗竭，以及生长调控基因表达层面的广泛改变。本研究利用RNA-Seq技术，对比了长骨（胫骨，1周龄与4周龄）中随年龄变化的基因表达特征，同时分析了1周龄时长骨与短骨（胫骨 vs 指骨）之间的基因表达差异。研究发现，短骨中的生长板衰老发育程序进展更为超前，而这种衰老差异（或衰老进程差异）正是骨骼长度差异的核心成因。