Abstract
The alveolar bone provides structural support against compressive and tensile forces generated during mastication as well as during orthodontic treatment. To avoid abnormal alveolar bone resorption and tooth loss, a balanced bone turnover by bone-degrading osteoclasts and bone-generating osteoblasts is of great relevance. Unlike its contradictory role in regulating osteoclast and osteoblast cell differentiation, the TGF-β/BMP-family member GDF15 is well known for its important functions in the regulation of cell metabolism, as well as cell fate and survival in response to cellular stress. Here, we provide first evidence for a potential role of GDF15 in translating mechanical stimuli into cellular changes in immature osteoblasts. We detected enhanced levels of GDF15 in vivo in periodontal ligament cells after the simulation of tooth movement in rat model system as well as in vitro in mechanically stressed human periodontal ligament fibroblasts. Moreover, mechanical stimulation enhanced GDF15 secretion by periodontal ligament cells and the stimulation of human primary osteoblast with GDF15 in vitro resulted in an increased transcription of osteogenic marker genes like RUNX2, osteocalcin (OCN) and alkaline phosphatase (ALP). Together, the present data emphasize for the first time a potential function of GDF15 in regulating differentiation programs of immature osteoblasts according to mechanical stimulation.
Highlights
Growth differentiation factor (GDF) 15 belongs to the transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) superfamily[19,20]
We asked whether GDF15 might have important functions in alveolar bone remodeling initiated through mechanical stimulation, which typically occur during mastication and Orthodontic tooth movement (OTM)
The TGF-β/BMP protein family is involved in the integration of mechanobiological signals, which is of major importance for the skeletal development as well as for bone homeostasis in adulthood and elderly[22,32]
Summary
Growth differentiation factor (GDF) 15 belongs to the transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) superfamily[19,20]. The relevance of many members of the TGF-β/BMP protein family in regulating bone development and metabolism has already been demonstrated in numerous studies (reviewed in Chen, et al.[21]). Some studies already showed that in myocardial and trabecular meshwork cells GDF15 expression depends on mechanical stimuli[29,30,31]. For this reason, we asked whether GDF15 might have important functions in alveolar bone remodeling initiated through mechanical stimulation, which typically occur during mastication and OTM. We examined a potential GDF15-dependent transcription of relevant osteogenic marker genes in primary osteoblasts stimulated with recombinant GDF15 protein
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