Theoretical stress analysis of organ culture osteogenesis

In a series of in vitro organ culture experiments by Klein-Nulend et al., intermittent ambient hydrostatic pressure was found to significantly increase the rate of calcification in the diaphysis of mouse rudiments while proteoglycan production was increased in the noncalcified epiphyses. In this study, we have conducted finite element stress analyses of this organ culture system in an effort to better understand the distribution of local tissue stresses which were created. Furthermore, we sought to clarify how these experimental results relate to our theory for skeletal morphogenesis which postulates that endochondral ossification is accelerated in regions of octahedral shear (deviatoric) stress and inhibited in areas of compressive hydrostatic (dilatational) stress. The results of the stress analyses show that externally applied hydrostatic pressure produces significant shear stresses at the cartilage/calcified cartilage interface and pure hydrostatic pressure at the rudiment ends. The accelerated osteogenesis in regions of high shear and the increased synthesis of proteoglycans in regions of high compressive hydrostatic stress are therefore consistent with our theory which predicts the regulation of cartilage maintenance and endochrondral ossification by intermittent tissue stresses.