Platelet-derived growth factor-BB regenerates functional periodontal ligament in the tooth replantation

Abstract

Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been proposed as a promising factor for preventing tooth ankylosis. Using rat tooth replantation model, we investigated whether PDGF-BB accelerates the repair of PDL after tooth replantation without ankylosis, and its molecular mechanisms. In PDGF-BB pretreated replanted teeth (PDGF-BB group), ankylosis was markedly reduced and functionally organized PDL collagen fibers were restored; the mechanical strength of the healing PDL was restored to an average of 76% of that in non-replanted normal teeth at 21 days. The numbers of PDGF-Rβ- and BrdU-positive cells in the periodontal tissues of the PDGF-BB group were greater than those of atelocollagen pretreated replanted teeth (AC group). Moreover, in the PDGF-BB group, the periodontal tissues had fewer osteocalcin-positive cells and decreased number of nuclear β-catenin-positive cells compared to those in the AC group. In vitro analyses showed that PDGF-BB increased the proliferation and migration of human periodontal fibroblasts. PDGF-BB downregulated mRNA expressions of RUNX2 and ALP, and inhibited upregulatory effects of Wnt3a on β-catenin, AXIN2, RUNX2, COL1A1, and ALP mRNA expressions. These findings indicate that in tooth replantation, topical PDGF-BB treatment enhances cell proliferation and migration, and inhibits canonical Wnt signaling activation in bone-tooth ankylosis, leading to occlusal loading of the PDL tissues and subsequent functional restoration of the healing PDL. This suggests a possible clinical application of PDGF-BB to reduce ankylosis after tooth replantation and promote proper regeneration of PDL.

Tooth transplantation and replantation: Biological insights towards therapeutic improvements

“…In pretreatment with BPs and PDGF‐BB, the mechanical strength increased to 67% and 76% of the control value, respectively. The extensibility, stiffness, and toughness of PDL tissue also increased in both treatments, suggesting their beneficial roles in recovering functional property and preventing ankylosis (Komatsu et al, 2022; Shibata et al, 2004).…”

“…In a rat replantation model, we recently showed that the topical application of PDGF‐BB to the root can effectively inhibit tooth ankylosis, which occurs frequently in control replantation. In PDGF‐BB‐pretreated replanted teeth, functionally organized PDL collagen fibers are restored, and the effects of PDGF‐BB on blocking ankylosis are mediated through the suppression of Wnt signaling (Komatsu et al, 2022).…”

Development and regeneration of periodontal supporting tissues

“…In periodontal tissue engineering, several growth and differentiation factors, including platelet‐derived growth factors (PDGFs), insulin‐like growth factors (IGFs), fibroblast growth factors (FGFs), transforming growth factor‐β (TGF‐β), enamel matrix protein, and bone morphogenetic proteins (BMPs) have been identified as potential therapeutic candidates to promote healing/regeneration of periodontal defects. PDGFs are mainly secreted by platelet alpha granules, besides platelets, macrophages, fibroblasts, myocytes, endothelial cells, and bone marrow hematopoietic cells also secrete PDGFs (Komatsu, Ideno, Shibata, Nakashima, & Nifuji, 2022). PDGFs exert their biological effects by binding to cell‐surface receptors (PDGFαR and ‐βR) with intrinsic tyrosine kinase activity that induce cells to undergo mitosis, chemotaxis, or matrix synthesis (Lee et al, 2000; Ripamonti, Crooks, Petit, & Rueger, 2001).…”

“…PDGFs exert their biological effects by binding to cell‐surface receptors (PDGFαR and ‐βR) with intrinsic tyrosine kinase activity that induce cells to undergo mitosis, chemotaxis, or matrix synthesis (Lee et al, 2000; Ripamonti, Crooks, Petit, & Rueger, 2001). In vitro experiments have shown that PDGF‐BB significantly increases the ALP activity of osteoblasts, as well as fibroblasts from PDL, cultured on collagen membrane (Komatsu et al, 2022). In a rat alveolar bone defect model, functionally graded material (a clinically available collagen membrane electrospun by a nanofibrous layer on the inner or outer surface) loaded with PDGF on the surface accelerates the regeneration of alveolar bone defect (Joshi, Padhye, & Gupta, 2019).…”

Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering

“…It comprises different, histologically defined tissues, i.e., the gingiva, the periodontal ligament (PDL), cementum, and the alveolar bone. Gingival fibroblasts (GFs) and gingival keratinocytes (GKs) are the main constituents of the gingiva, while the PDL, among other tissues, harbors specialized fibroblasts called periodontal ligament fibroblasts (PDLFs) and periodontal ligament stem cells (PDLSCs) [1][2][3][4]. The cementum is populated by cementoblasts, and the alveolar bone consists of osteoblasts, osteoclasts, mesenchymal stem cells (MSCs), and an organic as well as an inorganic matrix [5][6][7][8][9].…”