Conditional knockout of ephrinB1 in osteogenic progenitors delays the process of endochondral ossification during fracture repair

被引：6

作者：

Arthur, Agnieszka ^{[1
,2
]}

Paton, Sharon ^{[1
,2
]}

Zannettino, Andrew C. W. ^{[2
,3
]}

Gronthos, Stan ^{[1
,2
]}

机构：

[1] Univ Adelaide, Fac Hlth & Med Sci, Adelaide Med Sch, Mesenchymal Stem Cell Lab, Adelaide, SA 5001, Australia

[2] South Australian Hlth & Med Res Inst, Canc Theme, Adelaide, SA, Australia

[3] Univ Adelaide, Fac Hlth & Med Sci, Adelaide Med Sch, Myeloma Res Lab, Adelaide, SA, Australia

来源：

BONE | 2020年 / 132卷

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

Eph/ephrin receptor tyrosine kinases; Bone remodelling; Fracture repair; Osteoblasts; Osteoclasts; ANABOLIC RESPONSE; BONE-FORMATION; BISPHOSPHONATE INCADRONATE; CELL-DIFFERENTIATION; GENE-EXPRESSION; OSTERIX; INHIBITION; CLODRONATE; MUTATIONS; RECEPTORS;

D O I：

10.1016/j.bone.2019.115189

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The Eph receptor tyrosine kinase ligand, ephrinB1 (EfnB1) is important for correct skeletal and cartilage development, however, the role of EfnB1 in fracture repair is unknown. This study investigated the role of EfnB1 during fracture repair where EfnB1 expression increased significantly at 1 and 2 weeks post fracture in C57B1/6 wildtype mice, coinciding with the haematoma, soft callus formation/remodelling stages, respectively. To investigate the specific role of EfnB1 within the osteogenic lineage during fracture repair, male mice with a conditional deletion of EfnB1 in the osteogenic lineage (EfnB1(OB)(fl/O)), driven by the Osterix (Osx) promoter, and their male Osx:Cre counterparts were subject to a femoral fracture with internal fixation. Two weeks post fracture micro computed tomography (mu CT) analysis revealed that EfnB1(OB)(fl/O) mice displayed a significant decrease in bone volume relative to tissue volume within the fracture callus. This was attributed to an alteration in the distribution of osteoclasts within the fracture site, a significant elevation in cartilaginous tissue and reduction in the osteoprogenitor population and calcein labelled bone within the fracture site of EfnB1(OB)(fl/O) mice. Supportive in vitro studies demonstrated that under osteogenic conditions, cultured EfnB1(OB)(fl/O) stromal cells derived from the 2 week fracture site exhibited a reduced capacity to produce mineral and decreased expression of the osteogenic gene, Osterix, when compared to Osx:Cre controls. These findings suggest that the loss of EfnB1 delays the fracture repair process. The present study confirmed that EFNB1 activation in human BMSC, following stimulation with soluble-EphB2 resulted in de-phosphorylation of TAZ, demonstrating similarities in EfnB1 signalling between human and mouse stromal populations. Overall, the present study provides evidence that loss of EfnB1 in the osteo/chondrogenic lineages delays the soft callus formation/remodelling stages of the fracture repair process.

引用

页数：10

共 55 条

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