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DOI: 10.1055/s-0039-1700641
The role of mast cells in ovariectomy-induced delayed bone repair
Publication History
Publication Date:
14 November 2019 (online)
Introduction:
Mast cells (MCs) are important sensor and effector cells of the immune system which modulate both innate and adaptive immune responses. MCs are proposed to influence bone metabolism, since their number was found to be increased in patients with osteoporosis and inflammatory conditions affecting bone. Supporting, patients with systemic mastocytosis frequently display osteoporosis. Recently, we described that MCs stimulate osteoclastogenesis during fracture healing and ovariectomy-(OVX)-induced bone loss. Here, we investigated if MCs play a role during OVX-induced delayed bone healing.
Materials and methods:
Female C57BL/6J (WT) and Mcpt5-Cre R-DTA (MC-deficient: Cre+, MC-competent: Cre-) mice (3 – 4 months) were either OVX- or sham-operated and subjected to femur osteotomy. MC numbers and activity were assessed during bone healing in WT mice by immunohistochemical staining of Mcpt5 and gene expression analysis. Bone healing was evaluated in MC-competent and MC-deficient Mcpt5-Cre R-DTA mice at day 21 after fracture by biomechanical testing, µCT- and histomorphometric analyses (ANOVA/FisherLSD, p < 0.05).
Results:
WT-OVX mice displayed increased MC numbers in the fracture callus at day 3, 10 and 21 compared to sham mice. Gene expression of MC-specific markers MC-CPA3 and MCP4 was significantly increased in the callus of WT-OVX mice, thus indicating increased MC presence and activity. In MC-competent mice, OVX impaired bone healing as indicated by significantly reduced biomechanical competence, callus size, bone content and cortical bridging. Interestingly, MC-deficient OVX mice were protected against the OVX-induced delayed fracture healing.
Discussion:
These results indicate a significant role of MCs during OVX-induced delayed fracture healing and might lead to improving therapies for delayed osteoporotic bone healing. These results indicate a significant role of MCs during OVX-induced delayed fracture healing and might lead to improving therapies for delayed osteoporotic bone healing.
Key words:
Mast Cells, Osteoporosis, Fracture Healing