PI3K/AKT/mTOR signaling regulates BCP ceramic-induced osteogenesis

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Signaling

Background:

• Biphasic calcium phosphate (BCP) ceramics are known to induce bone regeneration.
• The precise molecular mechanisms underlying BCP-mediated osteogenesis remain unclear.

Purpose of the Study:

• To investigate the role of the PI3K/AKT/mTOR signaling pathway in BCP ceramic-induced osteogenesis.
• To elucidate how BCP ceramics influence mesenchymal stem cell behavior and bone formation.

Main Methods:

• Murine bone marrow-derived mesenchymal stem cells (BMSCs) were cultured with BCP ceramics.
• PI3K, AKT, and mTOR signaling pathways were inhibited using selective blockers.
• Gene expression (OPN, RUNX2, VEGF) and protein phosphorylation were analyzed.
• BCP ceramic implants were evaluated in vivo following intramuscular implantation in mice.

Main Results:

• BCP ceramics promoted BMSC proliferation in a time-dependent manner.
• BCP ceramics activated the PI3K/AKT/mTOR signaling pathway in BMSCs.
• Inhibition of PI3K/AKT/mTOR signaling abolished BCP-induced osteogenic differentiation and pro-angiogenesis.
• Blocking this pathway reduced stem cell infiltration and new bone formation in vivo.

Conclusions:

• The PI3K/AKT/mTOR signaling pathway is a critical regulator of BCP ceramic-induced osteogenesis.
• BCP ceramics leverage this pathway to enhance bone regeneration and vascularization.
• Targeting PI3K/AKT/mTOR signaling may offer therapeutic strategies for bone repair using BCP biomaterials.