Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells

Area of Science:

• Bone Biology
• Cellular Differentiation
• Metabolic Bone Diseases

Background:

• Advanced glycation end products (AGEs) disrupt bone remodeling, particularly in aging and diabetes.
• The precise role of AGEs in osteoclast-mediated bone resorption remains controversial.
• Understanding AGEs' stage-specific effects on osteoclasts is crucial for bone health.

Purpose of the Study:

• To investigate the differential effects of AGEs on osteoclast-like cells (OCLs) at distinct differentiation stages.
• To elucidate the mechanisms underlying AGEs' modulation of bone resorption.
• To clarify the controversial role of AGEs in bone resorption.

Main Methods:

• RAW264.7 cells were differentiated into OCLs, with stages identified by TRAP and CTSK levels.
• AGE-modified BSA or control BSA was added during either the cell fusion or mature stage.
• Bone resorption, cell morphology, and key protein expressions (RANK, CTSK) were analyzed.

Main Results:

• AGEs during the cell fusion stage significantly reduced bone resorption, decreasing pit formation, resorption area, CTSK, RANK expression, and OCL markers.
• AGEs during the mature stage markedly increased resorption area and pit numbers.
• Mature OCLs exposed to AGEs showed increased nuclei per OCL and podosome numbers.

Conclusions:

• AGEs exert biphasic modulation of OCL bone resorption dependent on differentiation stage.
• Early-stage AGEs inhibit bone resorption by suppressing RANK in precursors.
• Late-stage AGEs slightly enhance resorption, potentially via increased podosomes in mature OCLs.