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Real-Time Imaging of CCL5-Induced Migration of Periosteal Skeletal Stem Cells in Mice
Published on: September 16, 2020
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Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice
Verena Fischer1, Deniz Ragipoglu1, Johanna Diedrich1
1Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany.
Summary
Mast cells impair bone fracture healing in estrogen-deficient conditions, like osteoporosis. Targeting mast cells may improve bone repair in postmenopausal women.
Area of Science:
- Immunology
- Endocrinology
- Orthopedics
Background:
- Mast cells are immune cells implicated in osteoporosis.
- Estrogen deficiency, common in postmenopausal women, exacerbates bone loss and may affect fracture healing.
Purpose of the Study:
- To investigate the role of mast cells in impaired fracture healing under estrogen-deficient conditions.
- To elucidate the mechanisms by which mast cells affect bone repair.
Main Methods:
- Utilized mast cell-deficient mice (Mcpt5-Cre R-DTA) in an ovariectomy (OVX) model to assess fracture healing.
- Analyzed inflammatory mediators, immune cell infiltration, osteoblast and osteoclast activity, and serum RANKL levels.
- Conducted in vitro studies with human cells to examine mast cell-mediated osteoclastogenesis.
Main Results:
- Mast cell-deficient mice showed protected fracture healing after OVX.
- Mast cells promoted fracture site inflammation and neutrophil infiltration via mediators like IL-6, Mdk, and CXCL10.
- Mast cells reduced osteoblast activity and increased osteoclast activity and serum RANKL in OVX mice.
- Mast cells stimulated estrogen-dependent osteoclastogenesis via estrogen receptor alpha.
Conclusions:
- Mast cells negatively impact bone fracture healing in estrogen-deficient states.
- Targeting mast cells presents a potential therapeutic strategy for improving bone repair in postmenopausal osteoporosis.
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