Research Paper Volume 16, Issue 17 pp 12263—12276
Excessive glucocorticoids combined with RANKL promote the differentiation of bone marrow macrophages (BMM) into osteoclasts and accelerate the progression of osteoporosis by activating the SYK/SHP2/NF-κB signaling pathway
Figure 1. Effects of macrophage-specific knockout of SHP2 on ovariectomy-induced osteoporosis. (A) X-ray imaging was performed to assess bone density, bone quality, trabecular structure, and surface abnormalities in tibiae of mice from different experimental groups. SOP (ovariectomized) mice exhibited lower bone density, thinner bone quality, sparse trabeculae, and surface abnormalities compared to non-SOP mice. Conversely, SOP mice with macrophage-specific SHP2 knockdown (SOP+Lv-sh-SHP2) showed improved bone density, thicker bone quality, and preserved trabecular structure. (B) Hematoxylin and eosin (H&E) staining of vertebral sections revealed decreased cell numbers, enlarged gaps, and thinner trabeculae with fractures in SOP mice compared to non-SOP mice. However, SOP+Lv-sh-SHP2 mice displayed increased cell numbers and more continuous trabeculae. (C) Immunohistochemistry staining showed increased expression of phosphorylated SHP2 (p-SHP2) in SOP mice compared to non-SOP mice. Knockdown of SHP2 in macrophages resulted in decreased p-SHP2 expression, confirming successful knockdown. **P < 0.01.