Irisin Prevents Disuse-Induced Osteocyte Apoptosis

Area of Science:

• Bone Biology
• Cell Signaling
• Osteocyte Function

Background:

• Irisin improves bone mass and prevents osteoporosis.
• Osteocytes are mechanosensor cells crucial for bone health.
• Irisin's role in osteocyte survival and signaling is not fully understood.

Purpose of the Study:

• Investigate irisin's downstream signaling in osteocyte-like cells (MLO-Y4) in vitro.
• Analyze osteocyte survival and apoptosis in vivo in response to irisin.
• Elucidate the mechanisms of irisin action on osteocytes.

Main Methods:

• Treatment of MLO-Y4 cells with recombinant irisin (rec-irisin).
• Analysis of MAP kinases (Erk1/2) and transcription factor Atf4 expression.
• Assessment of Sost, Tfam, and Bcl2/Bax mRNA levels.
• In vivo studies using hindlimb-suspended mice treated with rec-irisin.
• Measurement of osteocyte viability, lacunae, and caspase activation (caspase-9, caspase-3).

Main Results:

• Rec-irisin activated Erk1/2 and increased Atf4 expression in MLO-Y4 cells.
• Intermittent irisin administration downregulated Sost mRNA.
• Irisin upregulated Tfam mRNA and increased the Bcl2/Bax ratio.
• Rec-irisin inhibited apoptosis induced by hydrogen peroxide and dexamethasone.
• In vivo, irisin prevented disuse-induced osteocyte loss and reduced caspase activation.

Conclusions:

• Irisin activates Erk-dependent pathways in osteocytes, modulating key gene expression.
• Irisin exerts anti-apoptotic effects on osteocytes through intrinsic and extrinsic pathways.
• Osteocytes are sensitive to irisin, suggesting a role for this myokine in bone health maintenance.
• Intermittent irisin administration shows specific effects on Sost expression.