Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.
Background: Limited evidence and contradictory results have been reported regarding the impact of tumor site on lymph node metastasis (LNM) and prognosis in T1 stage adenocarcinoma (AC). We aimed to compare two anatomic locations in terms of LNM and prognosis using a comprehensive statistical analysis of a large population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database and our center (First Affiliated Hospital of Nanchang University) were used to extract patient information. Univariate and multivariate logistic or Cox regression and propensity score matching were used to explore the association between LNM/survival and tumor site. Results: Information for 12,404 patients, including 9655 colonic AC and 2749 rectal AC patients, was extracted from the SEER database. The 516 AC patients included 184 colonic and 332 rectal AC patients from our center. Multivariate logistic regression analysis revealed a correlation between LNM and tumor site (colon vs rectum, odds ratio [OR] =1.52, 95% CI, 1.349-1.714, P<0.001). Additionally, we found that younger age, T1b stage, poor differentiation, and lymphatic invasion were risk factors for LNM. After adjusting for confounding factors by PSM, we found that the location of the rectum remained a higher risk factor for LNM. However, we found that patients diagnosed with rectal AC had a prognosis similar to that of patients diagnosed with colonic AC, which was demonstrated by the analysis of SEER data and data from our center. Conclusion: T1-stage rectal AC may have a higher risk of LNM than colonic AC, while rectal AC has a prognosis similar to that of colonic AC.
