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CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1/2 signaling pathway
Yang Yang1, Xinying Zhou1, Yuejun Li1
1Department of Orthopedics, Academy of Orthopedics Guangdong Province, the Third Affiliated Hospital of Southern Medical University, 510000 Guangzhou, China.
Abstract:
The C-X-C motif chemokine ligand 2 (CXCL2), a member of the CXC receptor ligand family, is involved in various immune and inflammatory processes, but its effect(s) on bone formation have not yet been reported. We report here that CXCL2 is enriched in bone marrow and show abundant expression of CXCL2 in osteoblasts of osteoporotic mice. CXCL2 neutralization within the bone marrow by using antibody alleviated bone loss in mice, indicating a negative role of CXCL2 in bone formation. In line with this, CXCL2 overexpression attenuated proliferation, as well as differentiation, of osteoblasts in vitro By contrast, CXCL2 downregulation promoted osteoblast expansion and differentiation. Mechanistically, CXCL2 inhibits the ERK1/2 (MAPK3/1) signaling pathway in osteoblasts. Activation of ERK1/2 abolishes the inhibitory effect of CXCL2 in osteoblasts, whereas inactivation of ERK1/2 reverses the osteogenic role of CXCL2 inhibition. These results show that CXCL2 attenuates osteoblast differentiation through inhibition of the ERK1/2 signaling pathway. We demonstrate here that CXCL2 is a negative regulator of bone formation and clarify the responsible mechanisms. Therefore, pharmaceutical coordination of CXCL2 and of the pathways through which it is regulated in osteoblasts might be beneficial regarding bone formation.
Insights
C-X-C motif chemokine ligand 2 (CXCL2) negatively regulates bone formation by inhibiting osteoblast differentiation via the ERK1/2 pathway. Targeting CXCL2 may improve bone health.
Area of Science:
- Bone Biology
- Immunology
- Cell Signaling
Background:
- C-X-C motif chemokine ligand 2 (CXCL2) is involved in immune and inflammatory processes.
- The role of CXCL2 in bone formation was previously unreported.
- CXCL2 is found in bone marrow and osteoblasts.
Purpose of the Study:
- To investigate the effect of CXCL2 on bone formation.
- To elucidate the underlying molecular mechanisms of CXCL2's action on osteoblasts.
Main Methods:
- CXCL2 neutralization in vivo using antibodies in mice.
- Osteoblast proliferation and differentiation assays in vitro.
- Analysis of the ERK1/2 (MAPK3/1) signaling pathway.
Main Results:
- CXCL2 neutralization alleviated bone loss in mice, indicating a negative role in bone formation.
- CXCL2 overexpression attenuated osteoblast proliferation and differentiation.
- CXCL2 inhibits osteoblast differentiation by suppressing the ERK1/2 signaling pathway.
Conclusions:
- CXCL2 is a negative regulator of bone formation.
- CXCL2 attenuates osteoblast differentiation via inhibition of the ERK1/2 pathway.
- Targeting CXCL2 and its regulatory pathways may offer therapeutic benefits for bone formation.
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