Antagonistic interplay between mechanical forces and glucocorticoids in bone: a tale of kinases

Area of Science:

• Bone biology
• Skeletal mechanobiology
• Cellular signaling

Background:

• Mechanical forces and glucocorticoids (GC) exert contrasting effects on bone.
• The precise cellular and molecular mechanisms underlying these skeletal impacts are not fully understood.
• Previous research highlighted divergent effects on osteocyte and osteoblast apoptosis.

Purpose of the Study:

• To review recent findings on the opposing actions of mechanical forces and GC on bone cell survival.
• To explore the role of focal adhesion kinases (FAKs) in mediating these effects.
• To hypothesize that similar opposing kinase signaling pathways influence other skeletal actions of mechanical forces and GC.

Main Methods:

• Review of existing literature on bone cell apoptosis, focal adhesion kinases, and skeletal regulation.
• Analysis of studies investigating the effects of mechanical stimuli and glucocorticoids on bone cells.
• Integrative approach to connect kinase signaling with broader skeletal processes.

Main Results:

• Mechanical forces and GC have converse effects on osteocyte and osteoblast survival.
• These opposing effects are mediated by differential regulation of focal adhesion kinases (FAK) and Pyk2.
• FAK and Pyk2 are key regulators of integrin-dependent cell-extracellular matrix interactions in bone.

Conclusions:

• Kinase signaling pathways involving FAK and Pyk2 are central to the opposing actions of mechanical forces and GC on bone cell survival.
• Similar opposing effects on kinase signaling may underlie other skeletal effects of these stimuli.
• This framework provides a basis for investigating the impact of mechanical forces and GC on bone formation and Wnt signaling.