Relaxin-2 promotes osteoblastic differentiation mediated by epidermal growth factor and epidermal growth factor receptor signaling.

Loss of osteogenic differentiation potential of osteoblasts has been associated with the pathogenesis of osteoporosis. Thus, stimulation of osteoblastic differentiation is a therapeutic strategy for osteoporosis. Relaxin-2 is a peptide hormone with potent biological functions. However, the effects of Relaxin-2 in osteoblastic differentiation and osteoporosis have not been reported before. Here, we report a novel physiological role of Relaxin-2 in promoting osteoblastic differentiation and mineralization of MC3T3-E1 cells. Our results indicate that exposure to Relaxin-2 upregulated the expression, and elevated the activity of alkaline phosphatase (ALP) when MC3T3-E1 cells were cultured in osteogenic differentiation medium (OM). Additionally, Relaxin-2 upregulated the mRNA levels of osteocalcin (ocn), osteopontin (opn), and collagen type I alpha 1 (Col1a1). The alizarin red S staining assay revealed that Relaxin-2 promoted the mineralization of MC3T3-E1 cells. We also found that Relaxin-2 increased the expression of Runx-2 as well as the epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Importantly, silencing of EGF abolished the effects of Relaxin-2 in osteoblastic differentiation and related gene expression. These findings suggest that Relaxin-2 stimulates osteogenic differentiation through activating EGF/EGFR signaling.

Gene Modification of Transforming Growth Factor ß (TGF-ß) and Interleukin 10 (IL-10) in Suppressing Mt Sonicate Induced Osteoclast Formation and Bone Absorption.

BACKGROUND Osteoarticular tuberculosis is an osteolytic lesion caused by Mycobacterium tuberculosis (MTB). Inflammatory factors such as TNF-α play a critical role in anti-tuberculosis immunity by regulating osteoblast and osteoclast functions. Both TGF-ß and IL-10 have immune suppression effects to downregulate secretion and release of inflammatory factors, such as TNF-α, that play roles in regulating osteoblast and osteoclast functions. This study thus investigated the effects of osteoclast with modified TGF-ß and IL-10 gene expression on MTB-induced osteoclast formation and bone absorption. MATERIAL AND METHODS Bone marrow mononuclear cells were induced to differentiate into osteoblasts and osteoclasts in vitro to generate a co-culture system. MTB powder lysed by ultrasound (Mt sonicate) were added in gradients to observe osteoblast formation and osteoclast absorption. Cell apoptosis was measured by flow cytometry, while ELISA was used assess TNF-α, TGF-ß, and IL-10. Viral vectors carrying TGF-ß or IL-10 gene were used to transfect osteoclasts, followed by ELISA assay. Bone absorption and osteoblast apoptosis were compared among groups. RESULTS Mt sonicate significantly facilitated osteoclast formation and bone formation. It upregulated contents of TNF-α, TGF-ß, and IL-10, induced osteoblast apoptosis, enhanced RANKL expression in osteoblasts, and decreased OPG expression. Overexpression of TGF-ß and/or IL-10 significantly decreased its upregulation effect on TNF-α by Mt sonicate, and hindered Mt sonicate-induced osteoblast apoptosis, osteoclast formation, and bone absorption. CONCLUSIONS Overexpression of TGF-ß and IL-10 significantly inhibits TMB-induced TNF-α synthesis and release, suppresses osteoblast apoptosis, and hinders osteoclast formation and bone absorption.

[Clinical application of neurovascular staghorn flap for repairing of defects in fingertips].

Objective: To evaluate the effectiveness of neurovascular staghorn flap for repairing defects in fingertips. Methods: Between August 2019 and October 2021, a total of 15 fingertips defects were repaired with neurovascular staghorn flap. There were 8 males and 7 females with an average age of 44 years (range, 28-65 years). The causes of injury included 8 cases of machine crush injury, 4 cases of heavy object crush injury, and 3 cases of cutting injury. There were 1 case of thumb, 5 cases of index finger, 6 cases of middle finger, 2 cases of ring finger, and 1 case of little finger. There were 12 cases in emergency, and 3 cases with finger tip necrosis after trauma suture. Bone and tendon exposed in all cases. The range of fingertip defect was 1.2 cm×0.8 cm to 1.8 cm×1.5 cm, and the range of skin flap was 2.0 cm×1.5 cm to 2.5 cm×2.0 cm. The donor site was sutured directly. Results: All flaps survived without infection or necrosis, and the incisions healed by first intention. All patients were followed up 6-12 months, with an average of 10 months. At last follow-up, the appearance of the flap was satisfactory, the wear resistance was good, the color was similar to the skin of the finger pulp, and there was no swelling; the two-point discrimination of the flap was 3-5 mm. One patient had linear scar contracture on the palmar side with slight limitation of flexion and extension, which had little effect on the function; the other patients had no obvious scar contracture, good flexion and extension of the fingers, and no dysfunction. The finger function was evaluated according to the total range of motion (TAM) system of the Hand Surgery Society of Chinese Medical Association, and excellent results were obtained in 13 cases and good results in 2 cases. Conclusion: The neurovascular staghorn flap is a simple and reliable method to repair fingertip defect. The flap has a good fit with the wound without wasting skin. The appearance and function of the finger are satisfactory after operation.

[Retracted] MicroRNA­130a inhibits growth and metastasis of osteosarcoma cells by directly targeting ZEB1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing cell migration assay data in Figs. 3B and C and 5C and D were strikingly similar to data appearing in different form in other articles by different authors. Furthermore, overlapping data panels were identified within this paper comparing the cell migration assay images between Figs. 3B and 5C. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 3606­3612, 2017; DOI: 10.3892/mmr.2017.6968].

MicroRNA­130a inhibits growth and metastasis of osteosarcoma cells by directly targeting ZEB1.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. microRNAs (miRNAs) have previously been reported to be involved in the carcinogenesis and progression of OS, and may be useful prognostic markers or therapeutic targets for patients with OS. miRNA­130a has been previously studied in multiple types of human cancer. However, its expression and function in OS has not been well documented. The aim of the present study was to investigate the expression, biological functions and molecular mechanisms underlying the effect of miR­130a in OS. miR­130a was significantly downregulated in OS tissues and cell lines compared with normal bone tissue and a normal osteoblast cell line. miR­130a expression levels was significantly negatively correlated with the clinical stage and metastasis of OS. Further studies indicated that overexpression of miR­130a inhibited OS cell proliferation, migration and invasion in vivo. In terms of the mechanisms underlying this effect, zinc finger E­box binding homeobox 1 (ZEB1) was demonstrated to act as a direct target of miR­130a in OS. Furthermore, downregulation of ZEB1 by interference with small interfering RNA mimicked the effects of transfection with an miR­130a mimic in OS. In conclusion, these results demonstrated that miR­130a functioned as a tumor suppressor in OS, partially via targeting ZEB1, suggesting that miR­130a may be considered as a target for the treatment of patients with OS.