M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis

Area of Science:

• Immunology
• Cell Biology
• Bone Biology

Background:

• Macrophages are key immune regulators with potential therapeutic roles in aging.
• Osteoporosis (OP) is a significant health concern, particularly in aging populations.
• Exosomes mediate intercellular communication and influence various physiological processes.

Purpose of the Study:

• To investigate the role of M1 macrophage-derived exosomes (M1Mφ-Exos) in osteoporosis development.
• To elucidate the involvement of microRNA-98 (miR-98) and dual specificity phosphatase 1 (DUSP1) in this process.

Main Methods:

• Established a murine model of osteoporosis using ovariectomy (OVX).
• Administered M1Mφ-Exos to OVX mice and cultured MC3T3-E1 osteoblast precursor cells.
• Utilized miRNA microarray analysis to identify differentially expressed miRNAs.
• Investigated the regulatory relationship between miR-98 and DUSP1.
• Assessed the impact of miR-98 and DUSP1 modulation on osteogenic differentiation and bone parameters.

Main Results:

• OVX mice exhibited reduced bone mineral density and trabecular bone number, indicative of bone loss.
• M1Mφ-Exos treatment exacerbated bone loss in OVX mice and suppressed osteogenic differentiation of MC3T3-E1 cells.
• miR-98 was significantly upregulated by M1Mφ-Exos, and DUSP1 was identified as a direct target of miR-98.
• Downregulation of miR-98 or upregulation of DUSP1 rescued osteogenic differentiation.
• Upregulation of DUSP1 reduced bone loss and JNK phosphorylation in vivo.

Conclusions:

• M1Mφ-derived exosomal miR-98 exacerbates bone loss and osteoporosis.
• This exacerbation occurs via downregulation of DUSP1 and subsequent activation of the JNK signaling pathway.
• miR-98 presents a potential therapeutic target for managing osteoporosis.