Transforming growth factor-beta (TGF-beta), one of the most abundant cytokines in bone matrix, has positive and negative effects on bone formation, although the molecular mechanisms of these effects are not fully understood. Bone morphogenetic proteins (BMPs), members of the TGF-beta superfamily, induce bone formation in vitro and in vivo. Here, we show that osteoblastic differentiation of mouse C2C12 cells was greatly enhanced by the TGF-beta type I receptor kinase inhibitor SB431542. Endogenous TGF-beta was found to be highly active, and induced expression of inhibitory Smads during the maturation phase of osteoblastic differentiation induced by BMP-4. SB431542 suppressed endogenous TGF-beta signaling and repressed the expression of inhibitory Smads during this period, possibly leading to acceleration of BMP signaling. SB431542 also induced the production of alkaline phosphatase and bone sialoprotein, and matrix mineralization of human mesenchymal stem cells. Thus, signaling cross-talk between BMP and TGF-beta pathways plays a crucial role in the regulation of osteoblastic differentiation, and TGF-beta inhibitors may be invaluable for the treatment of various bone diseases by accelerating BMP-induced osteogenesis.
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http://dx.doi.org/10.1038/sj.emboj.7600067 | DOI Listing |
Biogerontology
December 2024
Postgraduate Program in Pharmacology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, Brazil.
In cells, the term "cellular aging" represents a collection of biological changes that can precede the proliferative senescence states. Cells more resistant to proliferative senescence, such as the ones found in the basal layer of the epidermis, may also exhibit these aging patterns. Therefore, cellular aging events could be induced by endogenous signals named here as cellular aging triggers (CATs) components.
View Article and Find Full Text PDFMol Neurobiol
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Department of Emergency Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Astrocytes are abundant glial cells in the central nervous system (CNS) that play important roles in brain injury following cardiac arrest (CA). Following brain ischemia, astrocytes trigger endogenous neuroprotective mechanisms, such as fatty acid transport. Lipid droplets (LDs) are cellular structures involved in neutral lipid storage and play essential roles in many biological processes.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China.
The limited and backward diagnostic approaches elicit high mortality associated with pulmonary fibrosis (PF) because they fail to identify injury phase of PF. Developing a precisely theranostic nanoplatform presents a promising shortcut to reverse PF. Herein, a specific molecular nanotheranostic (Casp-GNMT), which is triggered by endogenous cysteinyl aspartate specific proteinase-3 (caspase-3), boosts antifibrotic efficacy through bioimaging synergistic with chemotherapy at molecular level, facilitating by ionizable lipid and reactive oxygen species sensitive lipid for precise and manageable therapy.
View Article and Find Full Text PDFCells
December 2024
Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, Germany.
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, due in part to early invasion and metastasis, which in turn involves epithelial-mesenchymal transition (EMT) of the cancer cells. Prompted by the discovery that two PDAC cell lines of the quasi-mesenchymal subtype (PANC-1, MIA PaCa-2) exhibit neuroendocrine differentiation (NED), we asked whether NED is associated with EMT. Using real-time PCR and immunoblotting, we initially verified endogenous expressions of various NED markers, i.
View Article and Find Full Text PDFACS Nano
December 2024
Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
Extracellular vesicles (EVs) possess the characteristics of their parent cells, based on which various studies have actively investigated treatments for diseases using mesenchymal stem cell-derived EVs due to their regenerative activity. Furthermore, in recent years, there have been significant efforts to engineer EVs to improve their native activities and integrate additional functions. Although both endogenous and exogenous methods are used for engineering EVs, endogenous methods may pose the problem of administering substances to cells undergoing metabolic changes, which can cause potential side effects.
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