Promotion of Kartogenin in tendon-bone healing of mouse model with rotator cuff tear repair and the mechanism
Objective To construct Kartogenin(KGN)-fibrin release system and to explore its effect and mechanism on tendon-bone healing of mouse model with rotator cuff tear repair.Methods KGN was loaded with fibrin sealant,and the release efficiency in vitro was determined by high performance liquid chromatography.Mice were divided into KGN group and control group with 36 mice in each group by random number table method.Mouse model with rotator cuff tear repair was constructed,and each mouse received unilateral supraspinatus tendon separation and bone repair.The control group was treated with fibrin no-load system at the tendone-bone repair site,while the KGN group was treated with KGN-fibrin release system at the tendone-bone repair site.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expressions of tendon remodeling and maturation-associated tenomodulin(TNMD),platelet-derived growth factor-AA(PDGFAA),sex-determing region of Y chromosome box transcription factor 9(SOX9),and SP7 transcription factor(SP7)mRNA in the shoulder of mice in two groups.Immunohistochemical staining was used to detect the levels of TNMD,PDGFAA,SOX9 and SP7 protein in shoulder joints of mice.HE and Alcian blue were used to observe fibrocartilage area,and Sirius red staining was used to observe density of collagen fibers.Results KGN in KGN-fibrin release system could be released for 5 days,and the release amount decreased with time,mainly in the previous 3 days,accounting for 34.29%of the total KGN in the released system.Compared with the control group,the relative mRNA expressions of TNMD,PDGFAA,SOX9,SP7 and the levels of corresponding proteins in tendon-bone tissue of mice in KGN group were up-regulated(all P<0.01).The area of fibrocartilage in KGN group was significantly smaller than that in the control group,while the density of collagen fibers was significantly increased.Conclusion KGN can promote tendon-bone healing of mouse model with rotator cuff tear repair,which may be achieved by promoting osteogenesis and tendon remodeling and maturation.