Abstract
Distraction osteogenesis (DO) is an efficient strategy that is employed for the treatment of large bone defects in craniomaxillofacial surgery. Despite its utility, however, DO is associated with a prolonged consolidation phase and a high complication rate that hinder its more widespread utilization. Panax notoginseng saponin (PNS) is a traditional Chinese medicine that is frequently administered for the treatment of a range of conditions. Herein, we explored the ability of PNS treatment to influence osteogenic differentiation using both rabbit bone marrow mesenchymal cells (BMSCs) and a model of mandibular DO. BMSC proliferation was assessed via CCK-8 assay, while osteogenic differentiation was monitored through ALP and alizarin red S staining. A PCR approach was used to evaluate the expression of genes associated with osteogenesis (ALP, Runx2, and OCN) and genes linked to the TGF pathway (TβR-II, SMAD2, SMAD3, and PPM1A). For in vivo experiments, treated BMSCs were locally injected into the DO gap, with PNS being injected into treated rabbits every other day throughout the experimental period. The quality of the regenerative process was assessed via scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray imaging, and hematoxylin and eosin (H&E) staining. These analyses revealed that PNS was able to promote BMSC osteogenesis and mandibular generation, driving the upregulation of osteogenesis-related genes at the mRNA levels through the modulation of the TGF-β1/Smad pathway. Consistently, the overexpression or silencing of TβR-II in PNS-treated BMSCs was sufficient to modulate their osteogenic potential. Analyses of in vivo mandibular DO outcomes revealed significantly augmented new bone growth in the PNS-treated group relative to control animals, with maximal osteogenesis in the group overexpressing rabbit TβR-II. Together, these results highlight the PNS as a promising and cost-effective therapeutic tool with the potential to enhance bone regeneration in clinical contexts through the modulation of the TGF-β1/Smad pathway.
Highlights
Segmental mandibular bone defects arising as a consequence of skeletal abnormalities, tumor resection, or trauma can impair chewing functionality, result in undesirable facial aesthetics, and engender mental health problems that make the treatment of such defects an important clinical challenge in the field of oral and maxillofacial surgery [1]
Average Distraction osteogenesis (DO) callus bone density was measured through X-ray imaging (Figures 1(d) and 1(e)), which indicated a significant increase in bone density in the Panax notoginseng saponin (PNS) group relative to the Ctrl group (p < 0.01) (Figures 1(f ) and 1(g))
hematoxylin and eosin (H&E) staining further revealed that the distraction gap region in rabbits from the saline treatment group was largely filled with fibrous tissue, whereas in the PNS treatment group, this region was bridged by newly formed immature bone trabecula (Figures 1(h) and 1(i))
Summary
Segmental mandibular bone defects arising as a consequence of skeletal abnormalities, tumor resection, or trauma can impair chewing functionality, result in undesirable facial aesthetics, and engender mental health problems that make the treatment of such defects an important clinical challenge in the field of oral and maxillofacial surgery [1]. Ere is an urgent clinical need for the development of novel approaches to shortening the DO consolidation phase in clinical settings. Stem cell-based therapeutic approaches have recently emerged as a promising approach to reducing DO-related complications by shortening the consolidation phase [4]. Mesenchymal stem cells (MSCs) are capable of undergoing self-renewal and differentiating into multiple cell types [5], and prior studies have explored their transplantation into damaged tissue sites in humans and animal models to facilitate tissue repair [6]. Despite the clinical promise of MSC-based therapeutic strategies, the limited survival rates and inefficient differentiation of these cells following their transplantation limit their therapeutic utility [8]
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