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FSTL3 mediates exercise driven bone formation.
Larsen M, Alisa Blazek, Agarwal S
Ohio State University
2015-03-15
Presenter: Michael T Larsen
Affidavit:
The resident performed all of the calvarial defects, implanting the scaffolds, and sewing up the defects on the mice. This represented about 15-20% of the project
Director Name: Gregory Pearson
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Hand
Introduction: Exercise is known to promote bone remodeling in bones that are directly biomechanically stimulated, yet little is known about its secondary effects at non-stimulated sites or the role of follistatin-like 3 (FSTL3; a mediator of exercise-driven bone formation) in this process.
Methods: Four millimeter diameter, calvarial defects were made in wild-type and FSTL3 knockout mice. Tissue engineered scaffolds containing bone marrow derived mesenchymal stem cells were placed in the defects and the incisions closed. Mice (n=5/gr) were either subjected to: (i) no treatment; (ii) gentle treadmill walking (TW; 7m/min for 45min/day); (iii) subcutaneous injection of BMP-2 (0.5 µg/mouse); or (iv) injection with FSTL3 (300 ng/mouse). The calvaria were harvested 6 or 12 weeks later and examined for bone formation by µCT, histology, and immunohistochemistry.
Results: TW induced significantly greater (4 ± 0.6 fold) vascularized bone formation. A 3.2 ± 0.7 fold increase in bone formation was observed in mice injected with FSTL3; likewise, a similar increase of bone formation (2.9 ± 0.6 fold) was observed in mice injected with BMP-2. Histologically, TW induced well-integrated bone in wild-type mice, but failed to induce bone formation in Fstl3 knockout mice.
Conclusions: Our data suggest that biomechanical stimulation is a potent inducer of bone formation, even in bones that are not directly stimulated. Patients could possibly benefit from prescribed exercise programs. Furthermore, the identification of FSTL3 as an inducer of bone formation provides a novel paradigm for future therapies aimed at augmenting bone formation.
