Muscle insulin-like growth factor-I modulates murine craniofacial bone growth

Abstract

Insulin-like growth factor I (IGF-I) is essential for muscle and bone development and a primary mediator of growth hormone (GH) actions. While studies have elucidated the importance of IGF-I specifically in muscle or bone development, few studies to date have evaluated the relationship between muscle and bone modulated by IGF-I in vivo, during post-natal growth. Mice with muscle-specific IGF-I overexpression (mIgf1+/+) were utilised to determine IGF-I- and muscle-mass-dependent effects on craniofacial skeleton development during post-natal growth. mIgf1+/+ mice displayed accelerated craniofacial bone growth when compared to wild-type animals. Virus-mediated expression of IGF-I targeting the masseter was performed to determine if post-natal modulation of IGF-I altered mandibular structures. Increased IGF-I in the masseter affected the mandibular base plane angle in a lateral manner, increasing the width of the mandible. At the cellular level, increased muscle IGF-I also accelerated cartilage thickness in the mandibular condyle. Importantly, mandibular length changes associated with increased IGF-I were not present in mice with genetic inhibition of muscle IGF-I receptor activity. These results demonstrated that muscle IGF-I could indirectly affect craniofacial growth through IGF-I-dependent increases in muscle hypertrophy. These findings have clinical implications when considering IGF-I as a therapeutic strategy for craniofacial disorders.

Ablation of specific insulin‐like growth factor I forms reveals the importance of cleavage for regenerative capacity and glycosylation for skeletal muscle storage

“…We focused on skeletal muscle even though all tissues respond to IGF-I and the mutations we generated may have different consequences. Whether or not bone density, [47][48][49][50] cognition, 51,52 or other parameters in any organ system are affected similarly to skeletal muscle is an open question. Furthermore, we have yet to examine the impact of IGF-I form loss in the context of muscle disease, where there can be heightened cycles of degeneration and regeneration leading to fibrotic replacement of functional muscle [53][54][55] ; aging, as the growth hormone/IGF-I axis diminishes with age 7,21 ; or in cancer, where highly active IGF-I forms may increase risk and severity.…”