Signaling Pathway and Transcriptional Regulation in Osteoblasts during Bone Healing: Direct Involvement of Hydroxyapatite as a Biomaterial

Abstract

Bone defects and periodontal disease are pathological conditions that may become neglected diseases if not treated properly. Hydroxyapatite (HA), along with tricalcium phosphate and bioglass ceramic, is a biomaterial widely applied to orthopedic and dental uses. The in vivo performance of HA is determined by the interaction between HA particles with bone cells, particularly the bone mineralizing cells osteoblasts. It has been reported that HA-induced osteoblastic differentiation by increasing the expression of osteogenic transcription factors. However, the pathway involved and the events that occur in the cell membrane have not been well understood and remain controversial. Advances in gene editing and the discovery of pharmacologic inhibitors assist researchers to better understand osteoblastic differentiation. This review summarizes the involvement of extracellular signal-regulated kinase (ERK), p38, Wnt, and bone morphogenetic protein 2 (BMP2) in osteoblastic cellular regulation induced by HA. These advances enhance the current understanding of the molecular mechanism of HA as a biomaterial. Moreover, they provide a better strategy for the design of HA to be utilized in bone engineering.

The Impact of the Extracellular Matrix Environment on Sost Expression by the MLO-Y4 Osteocyte Cell Line

“…The significant role of osteocytes in remodelling and mineral homeostasis has been well described [ 9 , 10 ]. Moreover, these data add to the growing evidence of HA as a bioactive molecule that has been shown to modulate expression of osteocyte proteins, such as Frizzled, Dickkopf, and Wnt, which are master regulators of the planar cell polarity and canonical pathways in osteocytes [ 38 ]. Therefore, it is clear that the addition of endogenous bone macromolecules in the form of a more ‘bone-like’ mimetic ECM has a significant effect upon osteocyte gene expression, and that such culture conditions, in the form of Coll-HA, can improve the power of the MLO-Y4 osteocyte model in emulating the primary osteocyte.…”

“…Bone demonstrates a unique three-dimensional ECM in the body. The main inorganic bone ECM element, hydroxyapatite (HA), has recently proven itself to not only act as a structural ECM component that confers strength and rigidity to bone, but also as a bioactive material [ 38 ]. Interestingly, HA has also been shown to modulate gene expression in osteocytes [ 39 ].…”

Melatonin enhances osteogenic differentiation of dental pulp mesenchymal stem cells by regulating MAPK pathways and promotes the efficiency of bone regeneration in calvarial bone defects

“…Thus, p-p38 and p-ERK are important mediators in the melatonin-mediated osteogenic differentiation of DPSCs. This is because MAPKs play a critical role in regulating MSC proliferation, differentiation, and apoptosis and are involved in multiple cellular signaling pathways [ 57 , 63 , 64 ].…”

Fabrication and Characterization of Submicron-Scale Bovine Hydroxyapatite: A Top-Down Approach for a Natural Biomaterial

“…Hydroxyapatite (HA) is a derivate of calcium phosphate that is widely used for medical purposes, including orthopedic and dental [ 16 ]. HA as a biomaterial can be synthesized from chemical precursors known as synthetic HA or extracted from natural sources such as mammalian bones [ 16 ]. One advantage in using natural HA compared to synthetic HA is the characteristics of natural HA.…”

“…Carbonated HA was found to increase osteoblast proliferation in vitro [ 20 ]. Other characteristics of BHA, such as its high compressive strength, prevent premature degradation and support bone formation in vivo [ 16 , 21 ].…”