Abstract
Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1+ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1+ cells, and we found that Gli1+ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP3R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1+ cells participate in mechanical force-induced osteogenesis through IP3R. Taken together, this study is the first to demonstrate that Gli1+ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP3R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.
Highlights
Skeletal malocclusion is the most severe type of malocclusion since it is difficult to correct by orthodontic methods in adults; skeletal malocclusion can be corrected using orthopedic force when the patient is at their growth peak with unclosed sutures [1]
It has been reported that unclosed maxillofacial sutures can be remodeled using orthopedic force, and maxillofacial sutures are the residence of mesenchymal stem cells (MSCs) which participate in maxillofacial bone development and damage repair [2, 3]
In order to investigate the role of Gli1+ cells in mechanical force-induced maxillofacial bone remodeling, we established a rapid maxillary expansion (RME) mouse model to imitate the procedure of orthodontic treatment of skeletal malocclusion using Gli1-LacZ transgenic mice to help detect Gli1+ cells after LacZ staining; as a control, we used mice that were not subjected to RME treatments (Supplementary Figure 1)
Summary
Skeletal malocclusion is the most severe type of malocclusion since it is difficult to correct by orthodontic methods in adults; skeletal malocclusion can be corrected using orthopedic force when the patient is at their growth peak with unclosed sutures [1]. It has been reported that unclosed maxillofacial sutures can be remodeled using orthopedic force, and maxillofacial sutures are the residence of mesenchymal stem cells (MSCs) which participate in maxillofacial bone development and damage repair [2, 3]. MSCs are commonly known to tend to osteogenesis after stimulation by mechanical stretching or incubation on stiff culture substrates [4,5,6,7]. It remains largely unclear whether MSCs that reside in maxillofacial sutures participate in orthopedic force-induced bone remodeling during skeletal malocclusion correction. Gli1+ cells, which are closely associated with osteogenesis and odontogenesis, are one of
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call