Effect of continuous dynamic pressure stress on experimental fracture healing and exploration of related signaling transduction pathways / 中国矫形外科杂志

ABSTRACT

[Objective]To evaluate the effect of continuous dynamic pressure stress on experimental humeral fracture healing and to explore the role of COX-2 /PGE2 /cAMP signaling pathway in healing promotion induced by the special biomechanical condition.[Method]A total of 120 New Zealand rabbits were divided randomly into three groups Group A,unilateral humeral fracture was fixed with shape memory connector(SMC),producing axial continuous dynamic pressure stress on fracture gap.Group B,fixed with 4-hole DCP,and Group C,fixed with SMC and gavaged with aqueous suspensions of celecoxib(3 mg/kg/day) after fracture.COX-1 and COX-2 mRNA expressions in fracture gap were determined by real-time RT-PCR at 0,3,7,14,21,28 and 56 days after operation,as well as the contents of PGE2 and cAMP were measured by radioimmunoassay(RIA).Bone-specific alkaline phosphatase(B-ALP) activity was determined by measuring p-nitrophenol and osteocalcin concentrations were measured using enzyme-linked immunosorbent assay(ELISA) for serial collected blood samples.Callus specimens fixed by formalin were used for histopathological examination.[Result]The COX-2 mRNA levels normalized with GAPDH mRNA as well as the contents of PGE2 and cAMP showed significant difference along with the 56-day period and also between the two internal fixations.Histopathological observation and determination of serum biochemical markers of bone formation revealed that the endochondral bone formation and the callus remodelling took place earlier in Group A than in Group B.The accelerated healing process and increased serum values of the bone formation markers induced by continuous dynamic pressure stress of SMC were inhibited by celecoxib,a specific COX-2 inhibitor.[Conclusion]The persistent dynamic longitudinal pressure stress produced by SMC contributed to endochondral bone formation and callus remodelling,resulting in an acceleration of fracture healing,which was considered to be closely correlated with the COX-2/PGE2/cAMP signal transduction pathway.