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.
Highlights
Hydroxyapatite (HA) is a biomaterial used for the production of orthopedic and dental implants
Pharmaceuticals 2021, 14, 615 factor Runt-related transcription factor 2 (Runx2) and its downstream osterix (Osx) [13,14], activating transcription factor 4 (ATF4) [15], distal-less homeobox 5 (Dlx5) [16], msh homeobox 1 (Msx-1) [17], and Msx-2 [18], and they are responsible for the expression of osteoblast proteins, including alkaline phosphatase (ALP) [19], collagen, and noncollagenous proteins [20,21,22,23,24,25]
These transcription factors are commonly used as markers in studies involving osteoblastic differentiation, including those related to the use of HA for bone regeneration [26,27,28]
Summary
Hydroxyapatite (HA) is a biomaterial used for the production of orthopedic and dental implants. Pharmaceuticals 2021, 14, 615 factor Runt-related transcription factor 2 (Runx2) and its downstream osterix (Osx) [13,14], activating transcription factor 4 (ATF4) [15], distal-less homeobox 5 (Dlx5) [16], msh homeobox 1 (Msx-1) [17], and Msx-2 [18], and they are responsible for the expression of osteoblast proteins, including alkaline phosphatase (ALP) [19], collagen, and noncollagenous proteins [20,21,22,23,24,25] These transcription factors are commonly used as markers in studies involving osteoblastic differentiation, including those related to the use of HA for bone regeneration [26,27,28]. Inactivation of Osx affects the expression of AT-rich sequence-binding protein 2 (Satb2) gene, which a transcription factor that regulates the differentiation of osteoblasts. Msx is a regulator of the OCN promoter [82] This transcription factor modulates the expression of various genes, including genes related to cholesterol synthesis during osteoblast differentiation from human dental pulp stem cells (DPSCs) [17]. These genes are upregulated by several biomaterials, and used as osteoinductive markers in vitro [86,87]
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