Postnatal Regulation of Bone Growth by Muscle IGF-1

Abstract

Interplay between muscle and bone is known to play an important role in growth modifications. Muscle loading from muscle hypertrophy promotes adjacent bone growth via Insulin-like Growth Factor-1 (IGF-1). Yet, in the absence of muscle hypertrophy, bone growth is not completely aborted indicating potential direct muscle paracrine role of muscle IGF-1 on bone. Maximizing growth potential and enhancing bone growth in mature bone in craniofacial skeleton is a significant benefit in orthodontic treatment. In this study, potential anabolic effect of muscle IGF-1 on post-natal mandibular growth is investigated. Methods: Four wild-type (WT) mice each at age of 6 weeks and 10 weeks; four dominant negative muscle specific IGF-1 receptor mice (MKR) each at age of 6 weeks and 10 weeks with one side masseter muscles injected with AAV-IGF-1 at 2 week of age were utilized. Four WT female and four WT male at age of 26 weeks with AAV-IGF-1 injection at age of 18 week were utilized. Muscle fiber size, mandibular bone lengths (sagittal and vertical) and condylar growth plate were evaluated from each animal. Results: Supplemental IGF-1 increased vertical mandibular bone growth in 6 weeks old MKR mice while 6 weeks old WT mice showed more increase in horizontal mandibular bone growth. There was no significant difference in mandibular growth in 10 weeks old WT and MKR mice. There was no significant effect of IGF-1 on muscle fiber size in both WT and MKR mice. Condylar growth plate analysis showed more mature form of chondrocytes with IGF-1 supplement. Conclusion: Post-natal muscle IGF-1 promoted bone growth in the absence of muscle hypertrophy

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