Sinomenine Inhibits Orthodontic Tooth Movement and Root Resorption in Rats and Enhances Osteogenic Differentiation of PDLSCs

Abstract

To investigate the effects of sinomenine on orthodontic tooth movement and root resorption in rats, as well as the effect of sinomenine on the osteogenesis of periodontal ligament stem cells (PDLSCs). Methods: Fifty-four male Wistar rats were randomly divided into 3 groups: control group, 20 mg/kg sinomenine group and 40 mg/kg sinomenine group. Fifty-gram orthodontic force was applied to all groups. Each group was injected intraperitoneally with corresponding concentration of sinomenine every day. After 14 days, all rats were sacrificed. Micro-computed tomography (micro-CT) scan was used to analyze tooth movement, root resorption and alveolar bone changes. The effect on periodontal tissue was analyzed by Masson, tartrate-resistant acid phosphatase (TRAP) and immunohistochemical staining. In vitro, PDLSCs were extracted and identified. The effect of sinomenine on proliferation was determined by cell-counting kit-8. The effect of sinomenine on osteogenesis was investigated by alkaline phosphatase (ALP) activity and alizarin red staining. qPCR and Western blotting were performed to explore the effects of sinomenine on the expression levels of ALP, runt-related transcription factor 2 (RUNX2), receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG). Results:The tooth movement and root resorption of sinomenine groups were reduced. Sinomenine decreased trabecular spacing on compression side and increased alveolar bone volume and trabecular thickness on tension side. TRAP-positive cells in sinomenine groups decreased significantly. The expressions of TNF-α and RANKL were decreased, while the expressions of OPG, RUNX2 and osteocalcin were up-regulated. In vitro, 0.1 M and 0.5 M sinomenine enhanced ALP activity, mineral deposition and the expression of ALP, RUNX2 and OPG, and reduced the expression of RANKL. Conclusion: Sinomenine could inhibit tooth movement, reduce root resorption, and exert a positive effect on bone formation in rats. Moreover, sinomenine promoted the osteogenesis of PDLSCs.

Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy

“…Zhang et al [ 29 ] reported that SIN decreased osteoclast differentiation or activity and reduced bone destruction in breast cancer patients. In a study on the treatment of orthodontic tooth movement and root resorption, Li et al [ 17 ] reported that SIN promoted the osteogenic differentiation of PDLSCs in vitro , but the study failed to further elucidate the specific mechanism by which SIN promotes the osteogenic differentiation of PDLSCs. However, these studies provide useful insight into SIN as a therapeutic option for osteoporosis.…”

“…Liao et al [ 16 ] concluded that SIN significantly alleviated arthritis symptoms in mice with collagen-induced arthritis by inhibiting proinflammatory cytokine secretion and inflammatory mediator production by synovial cells in arthritic mice and could decrease the formation, activity and survival of osteoclasts. SIN exerted beneficial therapeutic effects on periodontal erosive diseases and loose teeth both in vitro and in vivo by promoting the osteogenic differentiation of periodontal ligament stem cells (PDLSCs)[ 17 ]. However, there have been no reports on the effects of SIN in the treatment of osteoporosis, especially the specific mechanism by which SIN regulates the osteogenic differentiation of BMSCs.…”

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…Li et al reported that SIN (20 and 40 mg/kg) impeded orthodontic tooth movement (OTM) and root resorption, enhanced alveolar bone structure, increased bone volume/total volume (BV/TV), and decreased trap-positive osteoclasts on the compression side. SIN at concentrations of 0.1 M and 0.5 M augmented ALP activity, facilitated the deposition of mineralized nodules, upregulated OPG, ALP, and RUNX, and diminished RANKL in periodontal ligament stem cells (PDLSCs) [ 220 ]. In the same year, it was published that SIN promoted skin flap survival.…”

Scopolamine regulates the osteogenic differentiation of human periodontal ligament stem cells through lactylation modification of RUNX2 protein

“…Lactylation modification is known as a post‐translational regulatory mode, altering the protein stability 18 . Runt‐related transcription factor 2 (RUNX2) is an osteogenic gene, involving in the osteogenic differentiation of PDLSCs 19–21 . To date, it remains unclear whether SCO affects the lactylation‐mediated stability of RUNX2 in PDLSCs.…”

“… 18 Runt‐related transcription factor 2 (RUNX2) is an osteogenic gene, involving in the osteogenic differentiation of PDLSCs. 19 , 20 , 21 To date, it remains unclear whether SCO affects the lactylation‐mediated stability of RUNX2 in PDLSCs.…”