MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-beta/Smad pathway
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Authors: Hu, B-T; Chen, W-Z
OBJECTIVE: To explore whether MOTS-c could improve osteoporosis by promoting osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) via transforming growth factor-beta (TGF-beta)/Smad pathway. MATERIALS AND METHODS: Rat BMSCs were isolated and cultured, followed by osteogenic and lipid differentiation. CCK-8 (cell counting kit-8) assay was performed to detect the highest treatment dose of MOTS-c that did not affect cell proliferation. Expressions of osteogenesis-related genes (ALP. Bglap, and Runx2) were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction) and Western blot, respectively. Alizarin red staining and alkaline phosphatase (ALP) cytochemical staining were carried out to evaluate the effect of MOTS-c on BMSCs osteo-genesis. TGF-beta/Smad pathway-related genes (TGF-beta 1, TGF-beta 2, and Smad7) in BMSCs treated with MOTS-c were detected. Finally, TGF-beta 1 was knocked down to investigate the regulatory effect of MOTS-c on BMSCs osteogenesis. RESULTS: BMSCs exhibited an elongated morphology and was identified with a high purity by flow cytometry. After osteogenic differentiation. alizarin red staining and ALP staining were all positive. MOTS-c treatment could remarkably stimulate the formation of calcified nodules in BMSCs. Besides, TGF-beta/Smad pathway-related genes were significantly upregulated after BMSCs were treated with MOTS-c. Promoted osteogenesis by MOTS-c treatment was reversed by the TGF-beta 1 knockdown. CONCLUSIONS: MOTS-c promotes cell differentiation of BMSCs to osteoblasts via TGF-beta/ Smad pathway.
Arachidonic Acid: A Bridge between Traumatic Brain Injury and Fracture Healing
JOURNAL OF NEUROTRAUMA
Authors: Yang, Shuguang; Ma, Yanhong; Liu, Yong; Que, Haiping; Zhu, Changqiang; Liu, Shaojun
Traumatic brain injury (TBI) is associated with enhanced osteogenesis. The aim of this study was to investigate the effect of serum from TBI rats on fracture healing. Results from this study showed that the serum from TBI rats enhanced the expression of bone gamma carboxyglutamate protein (BGLAP), and promoted in vitro proliferation of MC3T3-E1 cells, a mouse osteoblastic cell line. Furthermore, gas chromatography/mass spectrometry (GC/MS) coupled with multivariate statistical analysis was used to identify the changes in global serum metabolites after TBI. We found that arachidonic acid (AA) was significantly enhanced in serum metabolites in TBI subjects, while hydroxybutyric acid, leucine, malic acid, 5-oxyproline, isocitric acid, mannose, and uric acid were reduced. Finally, we examined the effects of AA on BGLAP expression and cell proliferation in MC3T3-E1 cells. We found that BGLAP expression and proliferation of osteoblasts were positively regulated in the presence of AA. These findings suggest that the increased AA in serum after TBI may play a key role in enhancing the speed of fracture healing.