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International Journal of Molecular... Jul 2022The cranial base is formed by endochondral ossification and functions as a driver of anteroposterior cranial elongation and overall craniofacial growth. The cranial base... (Review)
Review
The cranial base is formed by endochondral ossification and functions as a driver of anteroposterior cranial elongation and overall craniofacial growth. The cranial base contains the synchondroses that are composed of opposite-facing layers of resting, proliferating and hypertrophic chondrocytes with unique developmental origins, both in the neural crest and mesoderm. In humans, premature ossification of the synchondroses causes midfacial hypoplasia, which commonly presents in patients with syndromic craniosynostoses and skeletal Class III malocclusion. Major signaling pathways and transcription factors that regulate the long bone growth plate-PTHrP-Ihh, FGF, Wnt, BMP signaling and Runx2-are also involved in the cranial base synchondrosis. Here, we provide an updated overview of the cranial base synchondrosis and the cell population within, as well as its molecular regulation, and further discuss future research opportunities to understand the unique function of this craniofacial skeletal structure.
Topics: Chondrocytes; Growth Plate; Head; Humans; Osteogenesis; Skull Base
PubMed: 35887171
DOI: 10.3390/ijms23147817 -
Molecules (Basel, Switzerland) Apr 2021Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review... (Review)
Review
Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker's yeast, as well as β-1,3-glucan from inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from and suppressed bone resorption in vivo. However, zymosan derived from stimulated the bone resorption activity and is widely used to induce arthritis in animal models. Additional research concerning the relationship between the molecular structure of β-glucan and its effect on osteoclastic bone resorption will be beneficial for the development of novel treatment strategies for bone-related diseases.
Topics: Animals; Bone Regeneration; Bone Resorption; Bone and Bones; Cartilage; Cell Differentiation; Glucans; Humans; Immunomodulation; Osteoclasts; Osteogenesis; Receptors, Immunologic
PubMed: 33915775
DOI: 10.3390/molecules26071982 -
Developmental Dynamics : An Official... Mar 2021Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and... (Review)
Review
Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and vocalization. The precise positioning, size, and shape of skeletal elements is therefore critical for their function. During embryonic development, bone forms by endochondral or intramembranous ossification and can arise from the paraxial and lateral plate mesoderm or neural crest. This review describes inductive mechanisms to position and pattern bones within the developing embryo, compares and contrasts the intrinsic vs extrinsic mechanisms of endochondral and intramembranous skeletal development, and details known cellular processes that precisely determine skeletal shape and size. Key cellular mechanisms are employed at distinct stages of ossification, many of which occur in response to mechanical cues (eg, joint formation) or preempting future load-bearing requirements. Rapid shape changes occur during cellular condensation and template establishment. Specialized cellular behaviors, such as chondrocyte hypertrophy in endochondral bone and secondary cartilage on intramembranous bones, also dramatically change template shape. Once ossification is complete, bone shape undergoes functional adaptation through (re)modeling. We also highlight how alterations in these cellular processes contribute to evolutionary change and how differences in the embryonic origin of bones can influence postnatal bone repair.
Topics: Animals; Bone and Bones; Cell Differentiation; Chondrocytes; Chondrogenesis; Humans; Osteoblasts; Osteogenesis
PubMed: 33314394
DOI: 10.1002/dvdy.278 -
Cell Proliferation Sep 2020Coupling between angiogenesis and osteogenesis has an important role in both normal bone injury repair and successful application of tissue-engineered bone for bone... (Review)
Review
Coupling between angiogenesis and osteogenesis has an important role in both normal bone injury repair and successful application of tissue-engineered bone for bone defect repair. Type H blood vessels are specialized microvascular components that are closely related to the speed of bone healing. Interactions between type H endothelial cells and osteoblasts, and high expression of CD31 and EMCN render the environment surrounding these blood vessels rich in factors conducive to osteogenesis and promote the coupling of angiogenesis and osteogenesis. Type H vessels are mainly distributed in the metaphysis of bone and densely surrounded by Runx2 and Osterix osteoprogenitors. Several other factors, including hypoxia-inducible factor-1α, Notch, platelet-derived growth factor type BB, and slit guidance ligand 3 are involved in the coupling of type H vessel formation and osteogenesis. In this review, we summarize the identification and distribution of type H vessels and describe the mechanism for type H vessel-mediated modulation of osteogenesis. Type H vessels provide new insights for detection of the molecular and cellular mechanisms that underlie the crosstalk between angiogenesis and osteogenesis. As a result, more feasible therapeutic approaches for treatment of bone defects by targeting type H vessels may be applied in the future.
Topics: Animals; Becaplermin; Blood Vessels; Bone Regeneration; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neovascularization, Physiologic; Osteoblasts; Osteogenesis; Receptors, Notch
PubMed: 33448495
DOI: 10.1111/cpr.12874 -
Clinical and Translational Medicine Feb 2022Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in... (Observational Study)
Observational Study
RATIONALE
Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context.
METHODS AND RESULTS
In patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α-SMA cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFβ1, phosphate and β-glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues.
CONCLUSION
We report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α-SMA regions of calcified cardiovascular tissues, induced by pro-inflammatory and pro-osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification.
Topics: Analysis of Variance; Cohort Studies; Cross-Sectional Studies; Extracellular Matrix Proteins; Humans; Linear Models; Muscle, Smooth; Netherlands; Osteogenesis; Prospective Studies; Proteoglycans; Statistics, Nonparametric; Sweden; Vascular Calcification
PubMed: 35184400
DOI: 10.1002/ctm2.682 -
Journal of Cellular Physiology Jan 2021Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone...
Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone-like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx-Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early-stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast-related gene expression and increased osteoclast-related gene expression in bone tissues, and reduced adipose tissue browning due to bone-born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gain-of-function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases.
Topics: Animals; Bone and Bones; Bone Diseases, Metabolic; Fibronectins; Muscle, Skeletal; Osteoblasts; Osteogenesis; Mice
PubMed: 32572964
DOI: 10.1002/jcp.29894 -
Theranostics 2023Large bone defects are a major global health concern. Bone tissue engineering (BTE) is the most promising alternative to avoid the drawbacks of autograft and allograft... (Review)
Review
Large bone defects are a major global health concern. Bone tissue engineering (BTE) is the most promising alternative to avoid the drawbacks of autograft and allograft bone. Nevertheless, how to precisely control stem cell osteogenic differentiation has been a long-standing puzzle. Compared with biochemical cues, physicomechanical stimuli have been widely studied for their biosafety and stability. The mechanical properties of various biomaterials (polymers, bioceramics, metal and alloys) become the main source of physicomechanical stimuli. By altering the stiffness, viscoelasticity, and topography of materials, mechanical stimuli with different strengths transmit into precise signals that mediate osteogenic differentiation. In addition, externally mechanical forces also play a critical role in promoting osteogenesis, such as compression stress, tensile stress, fluid shear stress and vibration, etc. When exposed to mechanical forces, mesenchymal stem cells (MSCs) differentiate into osteogenic lineages by sensing mechanical stimuli through mechanical sensors, including integrin and focal adhesions (FAs), cytoskeleton, primary cilium, ions channels, gap junction, and activating osteogenic-related mechanotransduction pathways, such as yes associated proteins (YAP)/TAZ, MAPK, Rho-GTPases, Wnt/β-catenin, TGFβ superfamily, Notch signaling. This review summarizes various biomaterials that transmit mechanical signals, physicomechanical stimuli that directly regulate MSCs differentiation, and the mechanical transduction mechanisms of MSCs. This review provides a deep and broad understanding of mechanical transduction mechanisms and discusses the challenges that remained in clinical translocation as well as the outlook for the future improvements.
Topics: Osteogenesis; Mechanotransduction, Cellular; Biocompatible Materials; Tissue Engineering; Mesenchymal Stem Cells; Cell Differentiation
PubMed: 37351163
DOI: 10.7150/thno.84759 -
Frontiers in Bioscience (Landmark... Feb 2022Orthodontic tooth movement (OTM) requires the orthodontic forces (compressive and tensile strain) to subject to the periodontal ligament and mechanosensory cells in the... (Review)
Review
Orthodontic tooth movement (OTM) requires the orthodontic forces (compressive and tensile strain) to subject to the periodontal ligament and mechanosensory cells in the periodontium and to achieve mechanotransduction by mechanoreceptors. In the context of OTM, a diverse array of signaling pathways are activated in mechanosensory cells that modulate bone resorption and formation in and models. The underlying molecular signal transduction, such as MAPK and β-Catenin signaling, that is involved in OTM, has been partially identified. It includes, but is not limited to genes and proteins which are related to osteogenesis, osteoclastogenesis, cementogenesis and inflammation. However, the interactive relation of β-Catenin and MAPK signaling remains ambiguous and diverse cross-talks are acting with each other. In this comprehensive text, we review the biology of OTM and reported experimental results on the activation/inhibition of these two signaling pathways during OTM. Here, we also focus on the implications and interplays between the MAPK and β-Catenin signaling in mechanosensory cells in response to orthodontic forces. Finally, the potential of further investigation strategies aimed at supporting orthodontic interventions are discussed. This review provides a conceptual framework for more comprehensive knowledge about signaling interaction during OTM.
Topics: Mechanotransduction, Cellular; Osteoclasts; Osteogenesis; Periodontal Ligament; Signal Transduction; Tooth Movement Techniques; beta Catenin
PubMed: 35226997
DOI: 10.31083/j.fbl2702054 -
ELife Oct 2019How does the skeleton detect and adapt to changes in the mechanical load it has to carry?
How does the skeleton detect and adapt to changes in the mechanical load it has to carry?
Topics: Ion Channels; Mechanotransduction, Cellular; Osteogenesis
PubMed: 31588900
DOI: 10.7554/eLife.50210 -
Nature Communications Nov 2022Although skeletal progenitors provide a reservoir for bone-forming osteoblasts, the major energy source for their osteogenesis remains unclear. Here, we demonstrate a...
Although skeletal progenitors provide a reservoir for bone-forming osteoblasts, the major energy source for their osteogenesis remains unclear. Here, we demonstrate a requirement for mitochondrial oxidative phosphorylation in the osteogenic commitment and differentiation of skeletal progenitors. Deletion of Evolutionarily Conserved Signaling Intermediate in Toll pathways (ECSIT) in skeletal progenitors hinders bone formation and regeneration, resulting in skeletal deformity, defects in the bone marrow niche and spontaneous fractures followed by persistent nonunion. Upon skeletal fracture, Ecsit-deficient skeletal progenitors migrate to adjacent skeletal muscle causing muscle atrophy. These phenotypes are intrinsic to ECSIT function in skeletal progenitors, as little skeletal abnormalities were observed in mice lacking Ecsit in committed osteoprogenitors or mature osteoblasts. Mechanistically, Ecsit deletion in skeletal progenitors impairs mitochondrial complex assembly and mitochondrial oxidative phosphorylation and elevates glycolysis. ECSIT-associated skeletal phenotypes were reversed by in vivo reconstitution with wild-type ECSIT expression, but not a mutant displaying defective mitochondrial localization. Collectively, these findings identify mitochondrial oxidative phosphorylation as the prominent energy-driving force for osteogenesis of skeletal progenitors, governing musculoskeletal integrity.
Topics: Mice; Animals; Oxidative Phosphorylation; Stem Cells; Signal Transduction; Osteogenesis; Cell Differentiation; Oxidative Stress; Adaptor Proteins, Signal Transducing
PubMed: 36369293
DOI: 10.1038/s41467-022-34694-8