Panax notoginseng Saponin Promotes Bone Regeneration in Distraction Osteogenesis via the TGF-β1 Signaling Pathway

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.

Overview of Physical and Pharmacological Therapy in Enhancing Bone Regeneration Formation During Distraction Osteogenesis

“…These analyses revealed that PNS was capable of enhancing mandibular generation and BMSC osteogenesis, upregulating osteogenesis-related genes at the mRNA levels through the modulation of the Smad/TGF-beta1 pathway. To sum up, these results proved the PNS as a potential and cost-effective therapeutic tool ( Liu et al, 2021 ). However, a single experiment lacks credibility, and further in-depth experiments are essential to confirm the relationship between PNS with DO.…”

Chromolaena odorata (L.) R. M. King and H. Robinson Leaves Aqueous Extract Improves the Femoral Head in Ethanol‐Induced Osteonecrosis in Rats

“…In fact, phytochemical screening of this extract revealed the presence of tannin, saponin, flavonoids, phenols, and coumarins [ 43 , 44 ]. Most of these biometabolites, such as flavonoid [ 45 , 46 ] and saponins [ 47 ], promote bone regeneration, while coumarins increase bone morphogenic protein-2 expression and thus enhance bone formation [ 48 ]. Moreover, these secondary metabolites particularly flavonoids, and phenols [ 49 , 50 ] are classes of compounds recognized for their ability to trap ROSs.…”

“…In fact, phytochemical screening of this extract revealed the presence of tannin, saponin, favonoids, phenols, and coumarins [43,44]. Most of these biometabolites, such as favonoid [45,46] and saponins [47], promote bone regeneration, while coumarins increase bone morphogenic protein-2 expression and thus enhance bone formation [48]. Moreover, these secondary metabolites particularly * p < 0.05, * * p < 0.01, and * * * p < 0.001: signifcantly diferent compared to the normal control group; a p < 0.05, c p < 0.001: signifcantly diferent compared to the alcohol control (1 or 2) group.…”