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Blockade of IL-6 alleviates bone loss induced by modeled microgravity in mice
Baorong He1, Xinhua Yin1, Dingjun Hao1,1
1Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Abstract:
This study investigated the effects of blockade of IL-6 on bone loss induced by modeled microgravity (MG). Adult male mice were exposed to hind-limb suspension (HLS) and treated with IL-6-neutralizing antibody (IL-6 nAb) for 4 weeks. HLS in mice led to upregulation of IL-6 expression in both sera and femurs. IL-6 nAb treatment in HLS mice significantly alleviated bone loss, evidenced by increased bone mineral density of whole tibia, trabecular thickness and number, bone volume fraction of proximal tibiae, and ultimate load and stiffness of femoral diaphysis. IL-6 nAb treatment in HLS mice significantly enhanced levels of osteocalcin in sera and reduced levels of deoxypyridinoline. In MC3T3-E1 cells exposed to MG in vitro, IL-6 nAb treatment increased mRNA expression and activity of alkaline phosphatase, mRNA expression of osteopontin and runt-related transcription factor 2, and protein levels of osteoprotegerin and decreased protein levels of receptor activator of the NF-κB ligand. In RAW254.7 cells exposed to MG, IL-6 nAb treatment downregulated mRNA expression of cathepsin K and tartrate-resistant acid phosphatase (TRAP) and reduced numbers of TRAP-positive multinucleated osteoclasts. In conclusion, blockade of IL-6 alleviated the bone loss induced by MG.
Insights
Blocking interleukin-6 (IL-6) with an IL-6-neutralizing antibody effectively prevents bone loss caused by modeled microgravity (MG) in mice. This targeted approach preserves bone mineral density and reduces markers of bone resorption.
Area of Science:
- Bone Biology
- Spaceflight Physiology
- Immunology
Background:
- Modeled microgravity (MG) induces significant bone loss, a critical concern for astronauts.
- Interleukin-6 (IL-6) expression is upregulated in response to MG, suggesting its involvement in bone resorption.
Purpose of the Study:
- To investigate the efficacy of blocking interleukin-6 (IL-6) in preventing bone loss induced by modeled microgravity (MG).
Main Methods:
- Adult male mice underwent hind-limb suspension (HLS) for 4 weeks, simulating MG.
- Mice were treated with an IL-6-neutralizing antibody (IL-6 nAb).
- In vitro studies used MC3T3-E1 and RAW254.7 cells exposed to MG.
Main Results:
- IL-6 nAb treatment significantly alleviated bone loss in HLS mice, improving bone mineral density and structural integrity.
- Treatment increased bone formation markers (osteocalcin) and decreased bone resorption markers (deoxypyridinoline).
- In vitro, IL-6 blockade promoted osteoblast differentiation and suppressed osteoclastogenesis.
Conclusions:
- Blockade of IL-6 is a promising therapeutic strategy to mitigate bone loss associated with microgravity.
- Targeting IL-6 can preserve bone health during spaceflight and other conditions causing bone demineralization.
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