Mechanical load regulates bone growth via periosteal Osteocrin

Area of Science:

• Bone Biology and Mechanobiology
• Endocrinology and Signaling

Background:

• Mechanical stimuli, such as loading, are known to promote bone growth after birth.
• The precise biochemical signaling pathways by which mechanical forces regulate bone growth remain incompletely understood.

Purpose of the Study:

• To identify novel mechanotransducers involved in load-induced long bone growth.
• To elucidate the molecular mechanisms by which mechanical stimuli regulate bone elongation and formation.

Main Methods:

• Identification and characterization of Osteocrin (OSTN), a novel secretory peptide.
• Investigation of OSTN's role in chondrocyte proliferation and maturation.
• Analysis of OSTN's interaction with C-type natriuretic peptide (CNP) and its receptor (NPR3).
• Examination of the regulation of Ostn expression by mechanical loading and the transcription factor FoxO1.

Main Results:

• Osteocrin (OSTN), produced by periosteal osteoblasts, acts as a mechanotransducer in load-induced long bone growth.
• OSTN enhances CNP-dependent chondrocyte proliferation and maturation, promoting long bone elongation.
• OSTN collaborates with CNP to stimulate osteogenic differentiation of periosteal osteoprogenitors.
• OSTN prevents CNP clearance by binding to NPR3, thereby facilitating CNP-mediated bone growth.
• Physiological loading upregulates Ostn expression in periosteal osteoblasts by suppressing FoxO1.

Conclusions:

• Osteocrin (OSTN) is a critical mediator translating mechanical loading into bone growth.
• The OSTN-CNP signaling axis plays a pivotal role in regulating both growth plate and bone formation.
• This study reveals a novel mechanism of mechanotransduction in bone development.