Stress amplification during development of the tendon-to-bone attachment.

Mechanical stress is necessary to sustain the mineral content of bone in adults. However, in a developing neonatal mouse, the mineralization of soft tissues progresses despite greatly reduced average mechanical stresses. In adults, these reduced loads would likely lead to bone loss. Although biochemical factors may partly explain these different responses, it is unclear how mineralization is initiated in low load environments. We present here the effect of morphometric data and initial modeling supporting a hypothesis that mechanical factors across several length scales amplify stresses, and we suggest that these stresses are of a level adequate to contribute to mechanical signaling for initiation of mineralization at the developing tendon-to-bone enthesis. A mineral gradient is evident across the insertion from the onset of mineralization. This grading maintains a constant size from early postnatal time points to adulthood. At the tissue level, this grading contributes to reduced stresses in an adult animal and to a minor elevation of stresses in a neonatal animal. At the cellular level, stress concentrations around mineralizing chondrocytes are enhanced in neonatal animals compared with adult animals. The enhancement of stresses around cells at early time points may serve to amplify and transduce low loads in order to initiate mineralization.