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Updated: Jan 3, 2026
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
CD11b promotes the differentiation of osteoclasts induced by RANKL through the spleen tyrosine kinase signalling
Guoxi Yang1, Xiaoyong Chen1, Zhao Yan1
1Institute of Orthopaedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Insights
Macrophage antigen-1 (CD11b) promotes osteoclast maturation by activating the Syk pathway. This finding is crucial for understanding osteolysis around artificial joints and developing targeted therapies.
Area of Science:
- Immunology
- Orthopedics
- Cell Biology
Background:
- Macrophage surface antigen-1 (Mac-1, CD11b/CD18) is linked to osteoclastogenesis.
- CD11b is upregulated in synovial tissues of patients with aseptic loosening after total hip replacement, suggesting a role in periprosthetic osteolysis.
Purpose of the Study:
- To investigate the specific role of CD11b and CD18 in osteoclast maturation and osteolysis.
- To elucidate the molecular mechanisms by which CD11b influences osteoclastogenesis.
Main Methods:
- Analysis of CD11b and CD18 expression in patient synovial tissues.
- Investigating the effect of CD11b on osteoclast precursors (OCPs) differentiation.
- Assessing the impact of CD11b on key signaling pathways, including Syk, c-Fos, NFATc1, and Erk.
- Evaluating the influence of ultra-high molecular weight polyethylene (UHMWPE) particles and TNF-α on CD11b levels.
Main Results:
- CD11b, but not CD18, was found to promote osteoclast (OC) maturation.
- CD11b upregulated spleen tyrosine kinase (Syk), c-Fos, NFATc1, and Erk activity, leading to OCP differentiation into tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts.
- Tumor necrosis factor-α (TNF-α) induced by UHMWPE particles increased CD11b levels.
Conclusions:
- CD11b acts as a positive regulator of osteoclastogenesis.
- CD11b mediates osteoclast maturation by activating the Syk signaling pathway.
- CD18 does not share the same regulatory role in osteoclastogenesis as CD11b.
Abstract:
Macrophage surface antigen-1 (Mac-1, CD11b/CD18) has been implicated in the regulation of osteoclastogenesis. In the synovial tissues of patients with aseptic loosening after total hip replacement, CD11b was up-regulated, which indicated that CD11b is closely involved in osteolysis around the prosthesis. We found that CD11b, but not CD18, promoted osteoclast (OC) maturation. Here, we show CD11b up-regulated the levels of spleen tyrosine kinase (Syk), c-Fos and nuclear factor of activated T cells, cytoplasmic-1 (NFATc1), as well as the activity of extracellular-regulated kinase (Erk), and as a result, osteoclast precursors (OCPs) differentiated and became tartrate-resistant acid phosphatase (TRAP)-positive. In addition, increased tumour necrosis factor-α (TNF-α) induced by ultra-high molecular weight polyethylene (UHMWPE) particles up-regulated the level of CD11b. Taken together, these findings suggest that CD11b is a positive regulator of osteoclastogenesis and that it functions by activating the Syk signalling pathway, while CD18 does not have the same effect.
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