Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma.

In recent decades, the stromal cell-derived factor-l (SDF-1) and Gab1 have been investigated to be involved in oncogenesis. However, it is scarcely reported that SDF-1-Gab1 pathway mediates proliferation and apoptosis in human chondrosarcoma (CS). In this study, we assessed the expression of Gab1 in 90 CS solid tumors by immunohistochemistry, immunoblotting, and qRT-PCR, and then, some in vitro assays were also applied to CS cells treated with SDF-1. We observed that the overexpression of Gab1 was positively correlated with lung metastasis and recurrence, and acts as an independent prognostic factor for CS patients. Gab1 expression was up-regulated in response to SDF-1 stimulation in CS cell line JJ012, SW1353, L3252. Overexpression of Gab1 increased Bcl-2/BAX ratio to promote cell growth via PI3K/AKT. On the other hand, silencing of Gab1 accelerated apoptosis and repressed the growth of CS cells, which further caused the inhibition of G1/S phase transition and decreased invasion capacity in CS cell lines. In vivo assay identified that the knockdown of Gab1 interfered with the tumor mass formation. In conclusion, our data identified overexpression of Gab1 in CS tissues, and Gab1 can be recommended as a novel biomarker for diagnosis and prognosis in patients with CS. Additionally, PI3K/AKT/Bcl-2/BAX axis was involved in Gab1-induced CS progression, indicating Gab1 might act as a new target for the treatment of CS patients.

Association between bone turnover markers, BMD and height loss of cemented vertebrae after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures.

INTRODUCTION: Percutaneous vertebroplasty (PVP) was recently performed for treating patients with osteoporotic vertebral compression fractures (OVCF). However, recompression of cemented vertebra with significant vertebral height loss occurred in the patients after PVP was observed during the follow-up period. The purpose is to explore the risk factors among several potential predictors for the height loss of treated vertebral bodies after PVP in patients with OVCF. METHODS: A study of 93 patients who had undergone PVP between May 1, 2016, and March 1, 2019, at the Spine Center of Huadong Hospital Affiliated to Fudan University was conducted. The fractured vertebral height loss ratio ≥ 15% at final follow-up were defined as cemented vertebra recompression. The following variables were measured and collected: age, gender, body mass index (BMI), bone mineral density (BMD), volume of bone cement injected, bone cement leakage, fractured vertebra segment, contact between bone cement and endplates, serum of calcium and phosphorus, and six kinds of bone turnover markers. RESULTS: Mann-Whitney U test and Univariate Logistic regression analysis showed that the cemented vertebra recompression was correlated with BMD, contact between bone cement and endplates, parathyroid hormone (PTH), and 25-hydroxy vitamin D3 (25-OH-D3). Following multivariate modeling, multiple factors logistic regression elucidated that high BMD (P < 0.001, OR = 0.089) and high level of serum 25-OH-D3 (P = 0.012, OR = 0.877) were negatively correlated with the cemented vertebra recompression after PVP. CONCLUSION: Decreased BMD and lower level of serum 25-OH-D3 might be two critical and significant risk factors for the height loss of cemented vertebrae after PVP.