Comparative analysis of bone turnover markers in bone marrow and peripheral blood: implications for osteoporosis.

INTRODUCTION: This study examines bone turnover marker (BTM) variations between bone marrow and peripheral blood in osteoporotic and non-osteoporotic patients. BTMs offer insights into bone remodeling, crucial for understanding osteoporosis. METHODS: A total of 133 patients were categorized into osteoporotic and non-osteoporotic cohorts. BTMs-C-telopeptide cross-linked type 1 collagen (ß-CTX), serum osteocalcin (OC), Procollagen type I N-propeptide (P1NP), 25(OH)D-were measured in bone marrow and peripheral blood. Lumbar spine bone mineral density (BMD) was assessed. RESULTS: Osteoporotic patients exhibited elevated ß-CTX and OC levels in peripheral blood, indicating heightened bone resorption and turnover. ß-CTX levels in osteoporotic bone marrow were significantly higher. Negative correlations were found between peripheral blood ß-CTX and OC levels and lumbar spine BMD, suggesting their potential as osteoporosis severity indicators. No such correlations were observed with bone marrow markers. When analyzing postmenopausal women separately, we obtained consistent results. CONCLUSIONS: Elevated ß-CTX and OC levels in osteoporotic peripheral blood highlight their diagnostic significance. Negative ß-CTX and OC-BMD correlations underscore their potential for assessing osteoporosis severity. Discrepancies between peripheral blood and bone marrow markers emphasize the need for further exploration. This research advances our understanding of BTM clinical applications in osteoporosis diagnosis and treatment.

eIF4E­related miR­320a and miR­340­5p inhibit endometrial carcinoma cell metastatic capability by preventing TGF­ß1­induced epithelial­mesenchymal transition.

Endometrial cancer (EC) is a common form of cancer in women. Metastasis is the main cause of EC treatment failure. Eukaryotic translation initiation factor 4E (eIF4E) is an oncogene that is overexpressed in a variety of malignancies and their distant metastases. The present study analyzed microarray data from the Oncomine database and revealed that high eIF4E expression was associated with poor prognosis and high pathological grade of EC. The expression of eIF4E was higher in EC tissues compared with in adjacent normal tissues. In addition, microRNA (miR)­320a and miR­340­5p expression levels were downregulated in EC tissues compared with those in adjacent normal tissues, which suggested that these microRNAs may serve as EC tumor suppressor genes. miR­320a and miR­340­5p could bind to the 3'­UTR of eIF4E mRNA, thus downregulating the expression of eIF4E and phosphorylated (p)­eIF4E in EC cells. Overexpression of miR­320a or miR­340­5p effectively suppressed HEC­1A cell migration and invasion. The downregulation of eIF4E and p­eIF4E following miR­320a or miR­340­5p transfection reduced the invasiveness and metastatic capability of EC cells in a manner associated with decreased expression of matrix metallopeptidase (MMP)­3 and MMP­9. In addition, one of the effects of transforming growth factor ß1 (TGF­ß1), which is to induce the phosphorylation of eIF4E, was suppressed by miR­320a and miR­340­5p overexpression. These two microRNAs also attenuated the features of TGF­ß1­induced epithelial­mesenchymal transition (EMT). In conclusion, the results of the present study demonstrated that eIF4E was upregulated in EC, whereas miR­320a and miR­340­5p were downregulated in EC compared with adjacent normal tissues. In vitro, miR­320a and miR­340­5p inhibited the migratory capability of EC cells by downregulating MMP­3 and MMP­9 and prevented TGF­ß1­induced EMT through p­eIF4E.

O­GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.

O­linked ß­N­acetylglucosamine (O­GlcNAc) modification is a dynamic post­translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling. This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O­GlcNAc transferase (OGT) and O­GlcNAcase (OGA), respectively. The present study aimed to determine the role of O­GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression. The results revealed that the expression of O­GlcNAc­modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry. Additionally, the level of endometrial O­GlcNAc modification increased gradually from the pre­receptive to the receptive phase, which was then decreased during the non­receptive phase. In endometrial cells, RNA interference was utilized to reduce the expression of two key O­GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O­GlcNAc modification. The results revealed that increasing the level of O­GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation. It is hypothesized that O­GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation. The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.