Effects of Bone Morphogenetic Proteins on TGF‐beta, Wnt and BMP Pathways During Tibial Fracture Repair

Our goal was to explore the effects of BMP2 and BMP7 on Bmp, Wnt, and TGFβ pathways during fracture repair. Tibial fractures were created in anesthetized mice, and Bmp2 or Bmp7 (or lactose as a control) was injected into the facture site (10μg). After injury, Bmp, Wnt and TGFβ pathway activity was assessed via immunochemical detection of pSMAD 1/5/8, beta‐catenin, or activation of Smad2/3‐luciferase transgene. pSmad 1/5/8 was expressed in chondrocytes (Ch) from days 5 to 21, and in osteoblasts (Ob) in new bone from days 7 to 21. In BMP2‐treated calluses, strong expression of pSmad 1/5/8 was detected in Ch from day 5 to 14 and in Ob from day 7 to 10. In BMP7‐treated calluses, pSmad 1/5/8 was weakly expressed in Ch from day 5 to 10 and was moderately expressed in Ob at day 10. Weak to moderate expression of β‐catenin was detected in Ch from day 5 to 10, and was moderately expressed in Ob at day 7. In BMP2‐treated calluses, β‐catenin was weakly expressed in Ch from day 5 to 10 and in Ob at day 10. In BMP7‐treated calluses, β‐catenin was moderately expressed in Ch from day 7 to 10; it was weakly expressed in Ob at day 7 and moderately expressed at day 10. Weak to moderate expression of luciferase was detected in Ch from day 5 to 21 and in Ob from day 7 to 21. In BMP2‐ treated calluses, luciferase was moderately expressed in Ch from day 5 to 21, and in Ob from day 7 to 21. In BMP7‐treated calluses, luciferase was weakly expressed in Ch at day 5 and moderately expressed from day 7 to 10; weak to moderate expression was detected in Ob from day 10 to 21. TGF‐β, Wnt and BMP pathways are activated in a unique temporal and spatial pattern during fracture repair. BMP and TGF‐β pathways appear to have synergistic effects on chondrogenesis, while BMP and Wnt pathways appear to have opposite effects on osteogenesis. Grant Funding Source : NIH