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Handbook of Experimental Pharmacology 2020Bone tissue is comprised of a collagen-rich matrix containing non-collagenous organic compounds, strengthened by mineral crystals. Bone strength reflects the amount and...
Bone tissue is comprised of a collagen-rich matrix containing non-collagenous organic compounds, strengthened by mineral crystals. Bone strength reflects the amount and structure of bone, as well as its quality. These qualities are determined and maintained by osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) on the surface of the bone and osteocytes embedded within the bone matrix. Bone development and growth also involves cartilage cells (chondrocytes). These cells do not act in isolation, but function in a coordinated manner, including co-ordination within each lineage, between the cells of bone, and between these cells and other cell types within the bone microenvironment. This chapter will briefly outline the cells of bone, their major functions, and some communication pathways responsible for controlling bone development and remodeling.
Topics: Bone Remodeling; Bone and Bones; Osteoblasts; Osteoclasts; Osteocytes
PubMed: 32006260
DOI: 10.1007/164_2019_343 -
Journal of Cellular and Molecular... Dec 2021Oxidative stress (OS)-induced mitochondrial damage and the subsequent osteoblast dysfunction contributes to the initiation and progression of osteoporosis....
Oxidative stress (OS)-induced mitochondrial damage and the subsequent osteoblast dysfunction contributes to the initiation and progression of osteoporosis. Notoginsenoside R1 (NGR1), isolated from Panax notoginseng, has potent antioxidant effects and has been widely used in traditional Chinese medicine. This study aimed to investigate the protective property and mechanism of NGR1 on oxidative-damaged osteoblast. Osteoblastic MC3T3-E1 cells were pretreated with NGR1 24 h before hydrogen peroxide administration simulating OS attack. Cell viability, apoptosis rate, osteogenic activity and markers of mitochondrial function were examined. The role of C-Jun N-terminal kinase (JNK) signalling pathway on oxidative injured osteoblast and mitochondrial function was also detected. Our data indicate that NGR1 (25 μM) could reduce apoptosis as well as restore osteoblast viability and osteogenic differentiation. NGR1 also reduced OS-induced mitochondrial ROS and restored mitochondrial membrane potential, adenosine triphosphate production and mitochondrial DNA copy number. NGR1 could block JNK pathway and antagonize the destructive effects of OS. JNK inhibitor (SP600125) mimicked the protective effects of NGR1while JNK agonist (Anisomycin) abolished it. These data indicated that NGR1 could significantly attenuate OS-induced mitochondrial damage and restore osteogenic differentiation of osteoblast via suppressing JNK signalling pathway activation, thus becoming a promising agent in treating osteoporosis.
Topics: Adenosine Triphosphate; Animals; Apoptosis; Biomarkers; Cell Line; Cell Survival; Ginsenosides; MAP Kinase Signaling System; Mice; Mitochondria; Osteoblasts; Oxidative Stress; Superoxides
PubMed: 34786818
DOI: 10.1111/jcmm.17054 -
Journal of Cellular and Molecular... Sep 2021LncRNAs and microRNAs play critical roles in osteoblast differentiation and bone formation. However, their exact roles in osteoblasts under fluid shear stress (FSS) and...
LncRNAs and microRNAs play critical roles in osteoblast differentiation and bone formation. However, their exact roles in osteoblasts under fluid shear stress (FSS) and the possible mechanisms remain unclear. The aim of this study was to explore whether and how miR-34a regulates osteoblast proliferation and apoptosis under FSS. In this study, FSS down-regulated miR-34a levels of MC3T3-E1 cells. MiR-34a up-regulation attenuated FSS-induced promotion of proliferation and suppression of apoptosis. Luciferase reporter assay revealed that miR-34a directly targeted FGFR1. Moreover, miR-34a regulated osteoblast proliferation and apoptosis via FGFR1. Further, we validated that lncRNA TUG1 acted as a competing endogenous RNA (ceRNA) to interact with miR-34a and up-regulate FGFR1 protein expression. Furthermore, lncRNA TUG1 could promote proliferation and inhibit apoptosis. Taken together, our study revealed the key role of the lncRNA TUG1/miR-34a/FGFR1 axis in FSS-regulated osteoblast proliferation and apoptosis and may provide potential therapeutic targets for osteoporosis.
Topics: Animals; Cell Differentiation; Cell Proliferation; HEK293 Cells; Humans; Mice; MicroRNAs; Osteoblasts; RNA, Long Noncoding; Receptor, Fibroblast Growth Factor, Type 1; Stress, Mechanical
PubMed: 34350720
DOI: 10.1111/jcmm.16829 -
Molecular Biology Reports Mar 2023This work compiles the characteristics of bone cells involved in the physiological bone remodeling. (Review)
Review
PURPOSE
This work compiles the characteristics of bone cells involved in the physiological bone remodeling.
METHODS
A narrative review of the literature was performed.
RESULTS
Remodeling is a different process from modeling. Remodeling allows old or damaged bone tissue to be renewed, ensuring the maintenance of bone fracture resistance, as well as maintaining calcium and phosphorus homeostasis. We present the role of osteoclasts, a multinucleated cell with hematopoietic origin responsible for resorbing bone. The formation of osteoclasts depends on the cytokines macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL) and can be blocked by osteoprotegerin. Furthermore, this review highlights the features of osteoblasts, polarized cubic cells of mesenchymal origin that deposit bone and also covers osteocytes and bone lining cells. This review presents the five fundamental phases of bone remodeling and addresses aspects of its regulation through hormones and growth factors.
CONCLUSIONS
Knowledge of the current concepts of physiological bone remodeling is necessary for the study of the different pathologies that affect the bone tissue and thus helps in the search for new therapies.
Topics: Osteocytes; Membrane Glycoproteins; Cell Differentiation; Carrier Proteins; Osteoclasts; Osteoblasts
PubMed: 36609750
DOI: 10.1007/s11033-022-08190-7 -
Materials Science & Engineering. C,... Apr 2020In this study, an in vitro evaluation of the human osteoblasts response to Organically Modified Silicate (ORMOSIL) biomaterials was conducted. These materials were...
In this study, an in vitro evaluation of the human osteoblasts response to Organically Modified Silicate (ORMOSIL) biomaterials was conducted. These materials were synthetized by sol-gel process being modified with zirconia (ZrO) and/or Ca. The materials were immersed into phosphate buffer solution (PBS) in order to test precipitation of mimetic apatite-like on their surfaces. ORMOSILs were characterized by SEM, FT-IR and X-RD analysis. The response of osteoblast to ORMOSILs was analyzed as a measure of cell adhesion, proliferation and differentiation. The results showed that the addition of Ca ions modifies the surface morphology of ORMOSILs by forming precipitates of mimetic apatite-like with cauliflower and scales morphologies. On the other hand, biological results suggest that the incorporation of zirconia to ORMOSILs increases their ability to support cell adhesion and proliferation. However, the inclusion of both zirconia and Ca in the ORMOSILs decreases their biological compatibility by showing less cell proliferation and lower osteonectin expression, a protein related to osteoblasts. The unfavorable effect of Ca on cell proliferation and cell viability could be due to its ability to induce the formation of mimetic apatite-like with incompatible morphology. The analysis of other proteins related to bone formation on ORMOSIL-Zr and ORMOSIL-Zr-Ca surfaces demonstrated clear expression of osteopontin and osteocalcin in cells growth. In the case of ORMOSIL-Zr, the expression of osteonectin occurred at early stages while the expression of osteopontin and osteocalcin begun at later stages, indicating a switch from an early to a mature stage being stimulated by the biomaterial. Together, these results highlight the important role of zirconia and Ca ions in the composition of materials regulating their biocompatibility when used as scaffolds in bone regeneration.
Topics: Bone Regeneration; Cell Adhesion; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Coated Materials, Biocompatible; Humans; Materials Testing; Osteoblasts; Tissue Scaffolds; Zirconium
PubMed: 32228947
DOI: 10.1016/j.msec.2019.110546 -
Biophysical Chemistry Dec 2020Based on the osteogenic effect, triiodothyronine (T3) plays an important role in bone growth and development. Autophagy contributes to osteoblast formation and...
Based on the osteogenic effect, triiodothyronine (T3) plays an important role in bone growth and development. Autophagy contributes to osteoblast formation and subsequent osteogenesis. Our study aims to explore the relationship among T3, autophagy and osteogenesis. In this study, cranial primary osteoblasts were obtained from 2 to 3 weeks-old Sprague Dawley (SD) rat fetuses. Osteoblasts were treated with T3, and then the autophagic parameters of Osteoblasts (including autophagic proteins, LC3 conversion rate and autophagosome formation) were observed through Western Blotting and Transmission Electron Microscopy. Next, after using autophagic pharmacological inhibitors (3-MA and chloroquine) and silencing vectors of autophagic genes (BECN1, Atg5 and Atg7) to downregulate autophagic activity, osteoblast proliferation and osteoblastic gene expression were detected using cell counting kit-8 (CCK-8) and quantitative real-time PCR (qRT-PCR) assays, respectively. Ultimately, the mice treated with partial thyroidectomy (PTx mice) were used to further observe the effect of T3 on the formation and autophagy of osteoblasts in trabecular bone in vivo. Our results show that T3 enhances osteoblast autophagy. Autophagy suppression with 3-MA, chloroquine or autophagy-genes knockdown reverses T3-promoted osteoblast formation. In vivo assays showed that the formation and autophagy of osteoblasts in bone tissue were reduced in T3-deficient young mice. Overall, T3 can promote osteoblast formation by activation of autophagy.
Topics: Animals; Autophagy; Cell Proliferation; Cells, Cultured; Mice; Mice, Inbred C57BL; Osteoblasts; Osteogenesis; Rats; Rats, Sprague-Dawley; Triiodothyronine
PubMed: 33010728
DOI: 10.1016/j.bpc.2020.106483 -
Journal of Cellular Physiology May 2021Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of...
Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of fractures. Thus, we hypothesized that osteoblasts, besides being negatively affected by interacting with adipocytes, reduce the differentiation of neighboring osteoblasts through the same mechanisms that affect osteoblasts under osteoporotic conditions. We investigated the effect of osteoporosis on osteoblast differentiation and the effect of the conditioned medium of osteoblasts cocultured with adipocytes on the differentiation of other osteoblasts. Osteoporosis was induced by orchiectomy in rats and bone marrow mesenchymal stromal cells (MSCs) were differentiated into osteoblasts. Also, the bone marrow and adipose tissue MSCs were obtained from healthy rats and differentiated into osteoblasts and adipocytes, respectively. Messenger RNA expression, in situ alkaline phosphatase activity, and mineralization confirmed the inhibitory effect of osteoporosis on osteoblast differentiation. This harmful effect was mimicked by the in vitro model using the conditioned medium and it was demonstrated that osteoblasts keep the memory of the negative impact of interacting with adipocytes, revealing an unknown mechanism relevant to the osteoporotic bone loss. Finally, we showed the involvement of acetyl-histone 3 (AcH3) in bone homeostasis as its reduction induced by osteoporosis and conditioned medium impaired osteoblast differentiation. The AcH3 involvement was proved by treating osteoblasts with Trichostatin A that recovered the AcH3 expression and osteoblast differentiation capacity in both situations. Together, our findings indicated that AcH3 might be a target for future studies focused on epigenetic-based therapies to treat bone diseases.
Topics: Acetylation; Adipocytes; Adipogenesis; Animals; Cell Differentiation; Coculture Techniques; Culture Media, Conditioned; Down-Regulation; Histones; Male; Models, Biological; Osteoblasts; Osteogenesis; Osteoporosis; Rats, Wistar; Rats
PubMed: 33124698
DOI: 10.1002/jcp.30131 -
Methods in Molecular Biology (Clifton,... 2020In the tissue culture dish, osteoblast cells can be derived from mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs) including embryonic stem cells (ESCs)...
In the tissue culture dish, osteoblast cells can be derived from mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, differentiation of osteoblasts from PSCs is time-consuming and low yield. In contrast, we identified four osteogenic transcription factors, Runx2, Osx, Dlx5, and ATF4, that rapidly and efficiently reprogram mouse fibroblasts derived from 2.3 kb type I collagen promoter-driven green fluorescent protein (Col2.3GFP) transgenic mice into induced osteoblast cells (iOBs). iOBs exhibit osteoblast morphology, form mineralized nodules, and express Col2.3GFP and gene markers of osteoblast differentiation. Our method provides a robust system to rapidly generate appropriate and abundant osteoblast cells for osteogenesis and bone regeneration study.
Topics: Animals; Biomarkers; Bone Regeneration; Calcification, Physiologic; Cell Culture Techniques; Cell Differentiation; Cell Separation; Cellular Reprogramming; Cellular Reprogramming Techniques; Fibroblasts; Genetic Vectors; Mice; Mice, Transgenic; Osteoblasts; Osteogenesis; Transduction, Genetic; Transgenes
PubMed: 32474879
DOI: 10.1007/978-1-0716-0655-1_17 -
Regulation of Hedgehog signaling Offers A Novel Perspective for Bone Homeostasis Disorder Treatment.International Journal of Molecular... Aug 2019The hedgehog (HH) signaling pathway is central to the regulation of bone development and homeostasis. HH signaling is not only involved in osteoblast differentiation... (Review)
Review
The hedgehog (HH) signaling pathway is central to the regulation of bone development and homeostasis. HH signaling is not only involved in osteoblast differentiation from bone marrow mesenchymal stem cells (BM-MSCs), but also acts upstream within osteoblasts via the OPG/RANK/RANKL axis to control the expression of RANKL. HH signaling has been found to up-regulate parathyroid hormone related protein (PTHrP) expression in osteoblasts, which in turn activates its downstream targets nuclear factor of activated T cells (NFAT) and cAMP responsive element binding protein (CREB), and as a result CREB and NFAT cooperatively increase RANKL expression and osteoclastogenesis. Osteoblasts must remain in balance with osteoclasts in order to avoid excessive bone formation or resorption, thereby maintaining bone homeostasis. This review systemically summarizes the mechanisms whereby HH signaling induces osteoblast development and controls RANKL expression through PTHrP in osteoblasts. Proper targeting of HH signaling may offer a therapeutic option for treating bone homeostasis disorders.
Topics: Animals; Hedgehog Proteins; Homeostasis; Humans; Osteoblasts; Osteoclasts; Osteogenesis; Parathyroid Hormone-Related Protein; RANK Ligand; Signal Transduction
PubMed: 31426273
DOI: 10.3390/ijms20163981 -
Journal of Bone and Mineral Metabolism Jan 2021Bone metastasis involves tumor-induced osteoclast activation, resulting in skeletal tumor progression as well as skeletal disorders. Aberrant expression of receptor... (Review)
Review
Bone metastasis involves tumor-induced osteoclast activation, resulting in skeletal tumor progression as well as skeletal disorders. Aberrant expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for osteoclast differentiation, induced by the metastatic tumor cells is responsible for the pathological bone resorption in bone metastasis. A fully human anti-RANKL neutralizing antibody has been developed to block osteoclast activation and is now used for the treatment of patients with bone metastasis and multiple myeloma. On the other hand, numerous studies have revealed that the RANKL/RANK system also contributes to primary tumorigenesis as well as metastasis through osteoclast-independent processes. Furthermore, emerging clinical and preclinical evidence has suggested anti-tumor immune effects of RANKL blockade when added to immune checkpoint inhibitor therapies. Study on the pleiotropic functions of RANKL in tumorigenesis and metastasis is now expanding beyond the bone field and has been established as one of the most important areas of "RANKL biology".
Topics: Animals; Bone Neoplasms; Carcinogenesis; Clinical Trials as Topic; Humans; Neoplasm Metastasis; Osteoblasts; RANK Ligand
PubMed: 33387063
DOI: 10.1007/s00774-020-01182-2