Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis

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.

Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review

“…They found that the calcium ion channel IP3R located on the endoplasmic reticulum was regulated by Gli + cells to promote osteogenesis. This study demonstrated that Gli1+ cells can sense mechanical forces and regulate calcium ion channels to modulate osteogenesis ( Huang et al, 2021 ). These reveal the specificity of Gli1+ in the process of skull reconstruction, providing a direction for skull reconstruction.…”

Transcriptomic and proteomic studies of condylar ossification of the temporomandibular joint in porcine embryos

“…Gli1 + cells gradually produce osteoblasts in all bone sites, and can mediate theTGF‐ß signaling pathway and play an important role in endochondral bone formation after fracture 28 . Some studies found that Gli1 + cells possess mechanical stress, which may regulate changes in intracellular Ca 2+ concentration through the inositol 1,4,5‐trisphosphate receptor (IP3R) to respond to mechanical force 29,30 . Compared with the above four genes, CLEC3B an CRABP2 have been less well studied in osteogenesis.…”

“…28 Some studies found that Gli1 + cells possess mechanical stress, which may regulate changes in intracellular Ca 2+ concentration through the inositol 1,4,5-trisphosphate receptor (IP3R) to respond to mechanical force. 29,30 Compared with the above four genes, CLEC3B an CRABP2 have been less well studied in osteogenesis. CLEC3B is a major structural protein of the ocular lens and is abundant in the kidney, central nervous system, skeletal muscle and heart.…”

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

“…Other P2Y receptors (P2Y12-13-14) also have connections to osteoblast and/or osteoclast activity [ 85 , 86 , 87 , 88 ]; however, their intracellular signalling is not mediated by IP 3 R, at least not in a direct manner. IP 3 Rs are known players of osteoblast [ 89 ] and Gli1 + cell [ 90 ] intracellular Ca 2+ homeostasis. There is also indirect evidence pointing at the importance of Ca 2+ release from the ER store via IP 3 R during bone formation.…”