Abstract
In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.
Highlights
It has been proposed that the discreet phases of bone repair in response to injury recapitulate those during development that give rise to the adult skeleton [1]
At 14d PO they were seen in residual connective tissue in the defect/medulla of WT mice (Fig 1, panel B2) and in marrow, usually adjacent to vascular channels at 28d and 56d PO (Fig 1, panels B3 and B4). acidified toluidine blue (aTB) positive cells were never seen in any of the bones harvested from Cpa3Cre/+ mice (Fig 1, panels C1 to C4)
The goal of the current study was to characterize the impact of mast cell deficiency on the repair of cortical bone defects using adult mast cell-deficient Cpa3Cre/+ mice
Summary
It has been proposed that the discreet phases of bone repair in response to injury recapitulate those during development that give rise to the adult skeleton [1]. In the long bones of the adult skeleton the bone healing cascade is initiated with a blood clot and an inflammatory response during which cells migrate to the site of injury [3]. Angiogenic factors attract vascular endothelial cells, which form vessels throughout the repair tissue. Bone anabolic agents such as Wnt ligands, parathyroid hormone (PTH) and related protein (PTHrP) and bone morphogenetic proteins (BMPs) induce differentiation of mesenchymal stromal cells (MSC) into osteoblasts. Woven bone is deposited by these cells in and around the soft callus to form a hard callus, which is remodeled by osteoclasts delivered through the new vessels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
