Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption.

Area of Science:

• Cell Biology
• Skeletal Biology
• Metabolic Homeostasis

Background:

• Osteolineage and myeloid cell interactions are vital for skeletal homeostasis.
• Mitochondrial function and transfer are increasingly recognized as critical cellular processes.

Purpose of the Study:

• To investigate the role of mitochondria transfer from osteolineage cells to myeloid cells in skeletal homeostasis.
• To elucidate the mechanisms by which impaired mitochondrial transfer affects bone metabolism and resorption.
• To explore the involvement of this process in glucocorticoid-induced osteoporosis.

Main Methods:

• Deletion of MIRO1 in osteolineage cells to impair mitochondrial transfer.
• Analysis of myeloid cell commitment toward osteoclastic lineage.
• Assessment of bone resorption markers.
• Investigation of glutathione metabolism and ferroptosis in osteoclastic lineage cells.
• Evaluation of glucocorticoid-induced osteoporosis models and the effect of glutathione depletion.

Main Results:

• Impaired mitochondrial transfer from osteolineage cells increases osteoclastic lineage cell commitment and bone resorption.
• Defective mitochondrial transfer alters glutathione metabolism, conferring resistance to ferroptosis in osteoclastic lineage cells.
• Mitochondrial transfer is implicated in the pathogenesis of glucocorticoid-induced osteoporosis.
• Glutathione depletion mitigates the progression of glucocorticoid-induced osteoporosis.

Conclusions:

• Osteolineage cells transfer mitochondria to myeloid cells, a process essential for maintaining skeletal metabolic homeostasis.
• This mitochondrial transfer regulates osteoclast differentiation and activity, influencing bone resorption.
• Disruption of mitochondrial transfer contributes to glucocorticoid-induced osteoporosis, highlighting glutathione metabolism as a therapeutic target.