Huabin Chen1, Zhanwen Wang1, Li Zhou1,2, Bing Wu1, Hongbin Lu1, Ciliu Zhang3, Tao Zhang1. 1. Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China. 2. Department of Orthopedic Center, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China. 3. Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
Abstract
BACKGROUND: Injuries of tendon-to-bone attachments (TBA) are common clinical challenges. Bone morphogenetic protein-4 (BMP-4) is potent in chondrogenesis. However, studies focusing on the influence of BMP-4 on the healing of TBA are scarce. Thus, this study's objective was to explore the effect of BMP-4 on the healing of TBA in a murine model of rotator cuff tear. METHODS: An injury model of the supraspinatus tendon (SST) insertion was established on a total of 120 mature C57 black (BL)/6 mice (12 weeks old), who were then randomly allocated into 3 groups: BMP-4, noggin (an inhibitor of all BMP activities), and control, At weeks 2 and 4 after surgery, the supraspinatus tendon-humerus complexes (SSTHC) were harvested for microradiographic, histologic, immunofluorescent, and biomechanical evaluations. RESULTS: Radiographic data showed that BMP-4 was able to improve the quality of subchondral bone, manifested as higher bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and lower trabecular spacing (Tb.Sp). Histologically, the BMP-4 group at week-2 and -4 showed a better TBA healing interface, characterized by better organizational integration and remodeling, thicker fibrocartilage layer, and more fibrocartilage cells. Immunofluorescence evaluation demonstrated that the number of SOX 9 positive cells in the BMP-4 group was significantly more than that in the control or noggin groups at postoperative weeks 2 and 4 (P<0.05 for all). Mechanical testing results at postoperative weeks 4 demonstrated the failure load, and stiffness in the BMP-4 group were significantly higher (P<0.05 for both), while in the noggin group were significantly lower (P<0.05 for both), compared to the control group. CONCLUSIONS: The BMP-4 might enhance TBA healing by promoting the regeneration of fibrocartilaginous enthesis and mineralization, while this process was inhibited by noggin. Thus, BMP-4 may be a potential therapy to augment TBA healing and finally lead to more rapid rehabilitation and reduce recurrent injury risk. 2021 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Injuries of tendon-to-bone attachments (TBA) are common clinical challenges. Bone morphogenetic protein-4 (BMP-4) is potent in chondrogenesis. However, studies focusing on the influence of BMP-4 on the healing of TBA are scarce. Thus, this study's objective was to explore the effect of BMP-4 on the healing of TBA in a murine model of rotator cuff tear. METHODS: An injury model of the supraspinatus tendon (SST) insertion was established on a total of 120 mature C57 black (BL)/6 mice (12 weeks old), who were then randomly allocated into 3 groups: BMP-4, noggin (an inhibitor of all BMP activities), and control, At weeks 2 and 4 after surgery, the supraspinatus tendon-humerus complexes (SSTHC) were harvested for microradiographic, histologic, immunofluorescent, and biomechanical evaluations. RESULTS: Radiographic data showed that BMP-4 was able to improve the quality of subchondral bone, manifested as higher bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and lower trabecular spacing (Tb.Sp). Histologically, the BMP-4 group at week-2 and -4 showed a better TBA healing interface, characterized by better organizational integration and remodeling, thicker fibrocartilage layer, and more fibrocartilage cells. Immunofluorescence evaluation demonstrated that the number of SOX 9 positive cells in the BMP-4 group was significantly more than that in the control or noggin groups at postoperative weeks 2 and 4 (P<0.05 for all). Mechanical testing results at postoperative weeks 4 demonstrated the failure load, and stiffness in the BMP-4 group were significantly higher (P<0.05 for both), while in the noggin group were significantly lower (P<0.05 for both), compared to the control group. CONCLUSIONS: The BMP-4 might enhance TBA healing by promoting the regeneration of fibrocartilaginous enthesis and mineralization, while this process was inhibited by noggin. Thus, BMP-4 may be a potential therapy to augment TBA healing and finally lead to more rapid rehabilitation and reduce recurrent injury risk. 2021 Annals of Translational Medicine. All rights reserved.
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