Abstract
Protease-activated receptor 1 (PAR1) has been associated to tissue repair and bone healing. The aim of the present study was to evaluate the effect of PAR1 activation on the osteogenic activity of human periodontal ligament stem cells (PDLSCs). PDLSCs were cultured in the presence of PAR1-selective agonist peptide (100 nM), thrombin (0.1 U/mL), or PAR1 antagonist peptide (100 nM). Calcium deposits, calcium concentration (supernatant), alkaline phosphatase activity (ALP), cell proliferation, and gene (qPCR) and protein expression (ELISA assay) of osteogenic factors were assessed at 2, 7, and 14 days. PAR1 activation led to increased calcium deposits (p < 0.05), calcium concentration (p < 0.05), ALP activity (p < 0.05), and cell proliferation (p < 0.05). Further, PAR1 activation may increase gene and protein expression of Runx2 (p < 0.05) and OPG (p < 0.05). In conclusion, PAR1 activation increases osteogenic activity of PDLSCs, providing a possible new strategy for periodontal regenerative therapies.
Highlights
Periodontitis is an inflammation of the periodontal tissues which results in the loss of alveolar bone and tissue attachment surrounding the teeth [1]
Seo et al [5] showed that when transplanted into periodontal defects surgically created in mice, Periodontal ligament stem cells (PDLSCs) can lead to periodontal ligament regeneration and may be associated with the trabecular bone regenerated in the periodontium, suggesting a potential role of PDLSCs in the regeneration of bone tissue
Protease-activated receptor 1 (PAR1) activation by its synthetic agonist peptide or thrombin resulted in significantly increased mineralized nodule formation compared to controls (p < 0 05)
Summary
Periodontitis is an inflammation of the periodontal tissues which results in the loss of alveolar bone and tissue attachment surrounding the teeth [1]. Periodontal ligament stem cells (PDLSCs) are able to differentiate into osteoblasts, cementoblasts, and fibroblasts and play an important role in the regeneration of periodontal tissues [4]. The proteolytic cleavage of PAR1 determines a new N-terminal sequence which binds to the receptor itself, resulting in its automatic activation, generating an intracellular signaling pattern [6]. PAR1 is expressed by several periodontal cell types, such as gingival epithelial cells [7], human gingival fibroblasts [8], osteoblasts [9], periodontal ligament cells [10], and monocytic cells [11], and its endogenous activators, such as thrombin, plasmin, and matrix metalloproteinases (MMPs), are present in the periodontium
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