The “mechanostat” principle in cell differentiation. The osteochondroprogenitor paradigm

Abstract

The "mechanostat" principle may be depicted as an oscillating signal of a signaling molecule, in which the amplitude, frequency, cumulative level, delay, and duration of the curve encode the information for concrete cellular responses and biological activities. When the oscillating signal is kept sustained (present delay), cell exit may be performed, whereas when the oscillating signal remains robust, cell proliferation may take place. B-catenin-Wnt signaling pathway has a key role in the differentiation of osteochondroprogenitor cells. Sustained downregulation of the β-catenin-Wnt pathway forces osteochondroprogenitors to a chondrogenic fate instead of an osteoblastic one. Other signaling, for example, bone morphogenetic protein and Notch signaling pathways interact with the Wnt pathway. The crosstalk between biochemical and mechanical stimuli produces the final information that leads to the final cell fate decisions, through the "mechanostat" principle.

β-catenin and Its Relation to Alveolar Bone Mechanical Deformation – A Study Conducted in Rats With Tooth Extraction

“…Frost introduced the "mechanostat theory" in bone biology to understand the "minimum effective strain (MES), " which relates bone architecture changes to mechanical loads (Tyrovola, 2019). In our study, the FEA was used in order to figure out about the bone tissue threshold for strain associated with the β-catenin activation in alveolar bone, and how is the behavior of the alveolar bone after induction of changes in mechanical stimulus on adjacent tooth (upper left incisor) due to tooth extraction.…”

“…It is established that Wnt plays an important role in the regulation of bone mass in humans and rodents, positively affecting bone formation by managing osteoblasts at different degrees, and it is recognized as an essential regulator of osteoblast activity through the translation of mechanical loading into biochemical signals (Baron and Rawadi, 2007;Tyrovola, 2019).…”