Ginsenoside Rg1 modulates PI3K/AKT pathway for enhanced osteogenesis via GPER.

BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by decreased bone density and the degradation of bone tissue microarchitecture. Ginsenoside Rg1, derived from Panax ginseng, has been a part of traditional Chinese medicine in China for centuries, particularly for treating osteoporosis. However, there remains limited research on the osteogenic potential of Rg1 within the glucocorticoid-induced osteoporosis (GIOP) model and its specific mechanisms. PURPOSE: The primary objective of this study is to investigate the osteogenic potential of Rg1 within the GIOP model and explore the signaling pathways associated with its in vivo and in vitro effects. METHODS: Cell proliferation, differentiation and mineralization were evaluated by the Cell counting kit 8(CCK8) assay, alkaline phosphatase (ALP) test and Alizarin Red S staining, respectively. The qPCR technique was used to determine the relative expression of mRNA and the western blot was used to determine the relative expression of protein. In vivo experiments, spinal vertebrae staining in zebrafish larvae was accomplished by alizarin red S staining. RESULTS: Zebrafish larvae's hatching, survival, malformation, and heart rate were unaffected by 50 µM of Rg1 in vivo, while the MEC3T3-E1 cell line's proliferation was unaffected by 50 µM of Rg1 in vitro. Meanwhile, Rg1 was shown to improve osteogenic differentiation or bone formation as well as the level of mRNA expression of osteogenic markers in vivo and in vitro. Treatment with Rg1 significantly increased the expression of G protein-coupled estrogen receptor (GPER) and pAKT. In addition, the GPER inhibitor G15 could significantly reduce the mRNA and protein expression levels of GPER and phosphorylated AKT, LY294002, a PI3K/AKT pathway inhibitor, markedly suppresses the expression of phosphorylated AKT, yet shows no significant impact on GPER expression. Both G15 and LY294002 can significantly blocked the Rg1-mediated enhancement of osteogenesis capacity in the GIOP model. In contrast, when both the agonists G1 of GPER and LY294002 were added, G1 increased the relative expression of mRNA and protein of GPER, but not the expression of osteogenic capacity and osteogenic markers. CONCLUSIONS: This study investigates the mineralization effects and mechanisms of Ginsenoside Rg1 both in vitro and in vivo. For the first time, we propose that Rg1 might regulate osteogenesis by modulating AKT phosphorylation through mediating GPER expression within the PI3K/AKT pathway in the GIOP model. This discovery introduces novel targets and avenues for osteoporosis treatment.

Dendrobium offificinale polysaccharides prevents glucocorticoids-induced osteoporosis by destabilizing KEAP1-NRF2 interaction.

Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale (D. officinale) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale, on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo, respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.

The Mysterious Role of Epidural Fat Tissue in Spine Surgery: A Comprehensive Descriptive Literature Review.

BACKGROUND: Though both neurosurgeons and orthopedic spinal surgeons are keenly aware of the clinical importance of epidural fat (EF), surgical practice varies amongst individual surgeons and across both fields. Thus, an in-depth understanding of the anatomical structure and composition of EF is vital, as it will play a significant role in the therapeutic management and the surgical choice of treatment. OBJECTIVE: We aim to extensively review the anatomical and biological properties of EF and further outline the surgical importance of EF management. STUDY METHODOLOGY: (i) MEDLINE search 1966-July 2019. Keywords: Review of the Literature. Authorship, Meta-analysis, Descriptive/Narrative overview; (ii) CINAHL search from 1982 to May 2019. Keywords: Review of the Literature spinal epidural fat; Authorship; Meta-analysis; Descriptive/Narrative overview; (iii) Hand searches of the references of retrieved literature; (iv) Personal and college libraries were searched for texts on research methods and literature reviews; and (v) 200 articles were downloaded, 50 were excluded because of similarity of topics and also because of new update on the same topics. (vi) Discussions with experts in the field of reviews of the literature. DISCUSSION: Though excessive or reductive amounts of EF usually exacerbates neurological symptoms and lead to various pathologic conditions such as spinal epidural lipomatosis, but there is no basic science, experimental, or clinical research that proves the role of EF in the aforementioned pathologic situations. CONCLUSION: Anatomical illustration, biological function and properties of EF knowledge may lead to changes in the stages of the surgical approach to avoid postoperative complications. However, the role of EF is exclusively bound to a scientific hypothesis as one cannot be sure if an excessive or reductive amount in EF is entirely responsible for the pathologic findings, or just only an incidental finding.

Retrospective analysis of deformed complex vertebral osteotomy in children with severe thoracic post-tubercular angular kyphosis.

BACKGROUND: Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. METHODS: Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. RESULTS: The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P < 0.001) with a mean kyphosis correction of 63.41°; at the final follow up, it was 18.4° ± 2.29° (P < 0.001) without obvious loss of correction. The postoperative mean TK, LL, and SVA were reduced to 24.05° ± 3.84°, 46.9° ± 3.53°, and 0.6 cm ± 0.34 cm, respectively (P < 0.001 for all); and there was no obvious loss of sagittal alignment and balance at the final follow up (p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P < 0.001); and ODI score reduced from 22.21 ± 6.93 to 5.02 ± 2.6 (P < 0.001) at the final follow up. CONCLUSIONS: DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (> 130°).

INTRODUCTION: The treatment of extremely severe and rigid spinal deformities was a great surgical challenge. Pulmonary impairment often occurred, which increased the challenges to already daunting surgical approaches. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction (HFT) for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (AIS) of more than 130°. MATERIALS AND METHODS: From 2010 to 2017, 11 patients suffered from extremely severe and rigid AIS of more than 130° underwent posterior-only surgical correction with HFT. The preoperative mean coronal Cobb angle of major curve was 139.01° ± 5.83°, and the mean flexibility was 17.21% ± 3.33%; the mean angle of thoracic kyphosis (TK) and lumbar lordosis (LL) were 65.02° ± 7.21° and 39.05° ± 4.08°, respectively; the mean trunk shift (TS) and sagittal vertical axis (SVA) were 3.3 ± 0.97 cm and 3.97 ± 1.16 cm, respectively; moreover, the percent forced vital capacity (FVC%) and percent forced expiratory volume in 1 s (FEV1%) were 50.08% ± 6.07% and 53.46% ± 5.96%, respectively; the mean body height and weight were 140.09 ± 4.95 cm and 37 ± 4.34 kg, respectively. RESULTS: The mean duration of surgery was 335.91 ± 48.31 min and blood loss was 1590 ± 520.1 ml. The average period of follow-up was 32.18 ± 8.17 months. After heavy HFT, the mean coronal Cobb angle of major curve was reduced to 82.98° ± 6.91° with correction rate of 40.39%. After posterior-only surgical correction, the mean coronal Cobb angle was further reduced to 51.17° ± 5.4° with correction rate of 63.27%. The postoperative mean TK, LL, TS and SVA were improved to 23.85° ± 5.14°, 44.95° ± 2.26°, 1.32 ± 0.72 cm and 1.42 ± 0.83 cm, respectively. At the final follow-up, the corrective loss rate of Cobb angle was only 0.72%; moreover, the mean FVC% and FEV1% were increased to 65.45% ± 5.29% and 69.08% ± 5.32% with improvement of 15.36% and 15.62%, respectively; the mean body height and weight were increased to 154.45 ± 5.32 cm and 45 ± 4.02 kg with improvement of 14.36 cm and 8 kg, respectively. The spinal cord function was stable, and there were no new neurological symptoms after correction. CONCLUSIONS: Posterior-only surgical correction with heavy HFT could be safe and effective for the treatment of extremely severe and rigid AIS of more than 130° in reducing the incidence of complications and greatly improving curve correction.

Posterior-Only Surgical Correction with Heavy Halo-Femoral Traction for the Treatment of Severe and Rigid Congenital Scoliosis Associated with Tethered Spinal Cord and Type II Split Cord Malformation.

OBJECTIVE: To evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction for the treatment of severe and rigid congenital scoliosis (SRCS) associated with tethered spinal cord (TSC) and type II split cord malformation (SCM). METHODS: Thirteen patients with SRCS associated with TSC and type II SCM underwent posterior-only surgical correction with heavy halo-femoral traction. The preoperative mean coronal Cobb angle was 88.87° ± 12.15°; the mean flexibility was 15.28% ± 3.88%; and the mean angle of thoracic kyphosis and lumbar lordosis was 39.63° ± 18.47° and 56.99° ± 10.02°, respectively. RESULTS: The mean duration of surgery was 320 ± 43.64 minutes and the mean blood loss was 1422.31 ± 457.59 mL. The mean follow-up period was 24.46 ± 7.53 months. After heavy halo-femoral traction, the mean coronal Cobb angle was reduced to 59.14° ± 8.75°. After posterior-only surgical correction, postoperative mean coronal Cobb angle was further reduced to 33.85° ± 8.77°. The postoperative mean correction rate was 62.46% ± 5.04%. The postoperative mean angle of thoracic kyphosis and lumbar lordosis was 29.31° ± 6.75° and 47.79° ± 3.68°, respectively. At the final follow-up, the corrective loss rate of Cobb angle was only 0.69%. There were no significant differences between final follow-up and preoperative modified Japanese Orthopaedic Association total scores. The Scoliosis Research Society-22 total score improved at the final follow-up evaluation compared with the preoperative total score. CONCLUSIONS: Without prophylactic neurosurgical intervention and spine-shortening osteotomy, posterior-only surgical correction with heavy halo-femoral traction could be safe and effective for the treatment of SRCS associated with TSC and type II SCM.