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Histology and Histopathology Oct 2021Hypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to their transient... (Review)
Review
Hypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to their transient nature. Historically, hypertrophic chondrocytes have been considered as the terminal state of growth plate chondrocytes, which are destined to meet their inevitable demise at the primary spongiosa. Chondrocyte hypertrophy is accompanied by increased organelle synthesis and rapid intracellular water uptake, which serve as the major drivers of longitudinal bone growth. This process is delicately regulated by major signaling pathways and their target genes, including growth hormone (GH), insulin growth factor-1 (IGF-1), indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic proteins (BMPs), sex determining region Y-box 9 (Sox9), runt-related transcription factors (Runx) and fibroblast growth factor receptors (FGFRs). Hypertrophic chondrocytes orchestrate endochondral ossification by regulating osteogenic-angiogenic and osteogenic-osteoclastic coupling through the production of vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix metallopeptidases-9/13 (MMP-9/13). Hypertrophic chondrocytes also indirectly regulate resorption of the cartilaginous extracellular matrix, by controlling formation of a special subtype of osteoclasts termed "chondroclasts". Notably, hypertrophic chondrocytes may possess innate potential for plasticity, reentering the cell cycle and differentiating into osteoblasts and other types of mesenchymal cells in the marrow space. We may be able to harness this unique plasticity for therapeutic purposes, for a variety of skeletal abnormalities and injuries. In this review, we discuss the morphological and molecular properties of hypertrophic chondrocytes, which carry out important functions during skeletal growth and regeneration.
Topics: Animals; Cell Size; Chondrocytes; Chondrogenesis; Growth Plate; Humans; Osteogenesis
PubMed: 34137454
DOI: 10.14670/HH-18-355 -
Advanced Healthcare Materials Oct 2020Mechanical signals play a central role in cell fate determination and differentiation in both physiologic and pathologic circumstances. Such signals may be delivered... (Review)
Review
Mechanical signals play a central role in cell fate determination and differentiation in both physiologic and pathologic circumstances. Such signals may be delivered using materials to generate discrete microenvironments for the purposes of tissue regeneration and have garnered increasing attention in recent years. Unlike the addition of progenitor cells or growth factors, delivery of a microenvironment is particularly attractive in that it may reduce the known untoward consequences of the former two strategies, such as excessive proliferation and potential malignant transformation. Additionally, the ability to spatially modulate the fabrication of materials allows for the creation of multiple microenvironments, particularly attractive for regenerating complex tissues. While many regenerative materials have been developed and tested for augmentation of specific cellular responses, the intersection between cell biology and material interactions have been difficult to dissect due to the complexity of both physical and chemical interactions. Specifically, modulating materials to target individual signaling pathways is an avenue of interdisciplinary research that may lead to a more effective method of optimizing regenerative materials. In this work, the aim is to summarize the major mechanotransduction pathways for osteogenic differentiation and to consolidate the known materials and material properties that activate such pathways.
Topics: Cell Differentiation; Mechanotransduction, Cellular; Osteogenesis; Signal Transduction; Stem Cells
PubMed: 32940024
DOI: 10.1002/adhm.202000709 -
BMC Oral Health Oct 2021Periodontitis is the most extensive chronic inflammatory bone resorption disease. MiRNAs offer a potential way for potential therapy. Indeed, miR-30a-5p had an...
BACKGROUND
Periodontitis is the most extensive chronic inflammatory bone resorption disease. MiRNAs offer a potential way for potential therapy. Indeed, miR-30a-5p had an increasing expression in periodontitis gingivae, but whether it promotes osteogenesis and inhibits inflammation remains unknown.
METHODS
Periodontitis model was exhibited by wire ligation and verified by micro-CT and HE staining; qPCR was used to detect the expression of miR-30a-5p; miR-30a-5p inhibitors and mimics were transfected into MC3T3-E1 cell line by lipofectamine 3000; The dual luciferase reporter gene experiment and RIP experiment were used to detect the relationship between miR-30a-5p and Runx2; Rescue experiment was used to verify the relationship between miR-30a-5p and Runx2.
RESULTS
Periodontitis model was exhibited successfully and miR-30a-5p was overexpressed at the bone and gingival tissues of this model. miR-30a-5p inhibitors not only promoted the osteogenesis but also relieved inflammation. Runx2 is a target of miR-30a-5p by dual luciferase reporter gene experiment and RIP experiment. Rescue experiments revealed that miR-30a-5p inhibitors would promote osteogenesis and relieve inflammation by targeting Runx2 in inflammation of MC3T3-E1 cell line.
CONCLUSIONS
That all suggested that miR-30a-5p-mediated-Runx2 provided a novel understanding of mechanism of periodontitis.
Topics: 3T3 Cells; Animals; Cell Line; Core Binding Factor Alpha 1 Subunit; Mice; MicroRNAs; Osteogenesis; Periodontitis
PubMed: 34635105
DOI: 10.1186/s12903-021-01882-9 -
Histology and Histopathology Feb 2022Due to their immunoregulatory properties and capacity for multi-lineage differentiation, mesenchymal stem cells (MSCs) have been used as new therapeutic agents in... (Review)
Review
Due to their immunoregulatory properties and capacity for multi-lineage differentiation, mesenchymal stem cells (MSCs) have been used as new therapeutic agents in regenerative medicine. Numerous lifestyle habits and behavioral risk factors may modulate metabolic and cell growth signaling pathways in MSCs, affecting their phenotype and function. Accordingly, identification of these factors and minimization of their influence on viability and function of transplanted MSCs may greatly contribute to their better therapeutic efficacy. A large number of experimental and clinical studies have demonstrated the detrimental effects of cigarette smoke and nicotine on proliferation, homing, chondrogenic and osteogenic differentiation of MSCs. Cigarette smoke down-regulates expression of chemokine receptors and modulates activity of anti-oxidative enzymes in MSCs, while nicotine impairs synthesis of transcriptional factors that regulate the cell cycle, metabolism, migration, chondrogenesis and osteogenesis. In this review article, we summarize current knowledge about molecular mechanisms that are responsible for cigarette smoke and nicotine-dependent modulation of MSCs' therapeutic potential.
Topics: Cell Differentiation; Chondrogenesis; Cigarette Smoking; Mesenchymal Stem Cells; Nicotine; Osteogenesis
PubMed: 34845711
DOI: 10.14670/HH-18-400 -
Stem Cells (Dayton, Ohio) Sep 2023Numerous intrinsic factors regulate mesenchymal progenitor commitment to a specific cell fate, such as osteogenic or adipogenic lineages. Identification and modulation...
Numerous intrinsic factors regulate mesenchymal progenitor commitment to a specific cell fate, such as osteogenic or adipogenic lineages. Identification and modulation of novel intrinsic regulatory factors represent an opportunity to harness the regenerative potential of mesenchymal progenitors. In the present study, the transcription factor (TF) ZIC1 was identified to be differentially expressed among adipose compared with skeletal-derived mesenchymal progenitor cells. We observed that ZIC1 overexpression in human mesenchymal progenitors promotes osteogenesis and prevents adipogenesis. ZIC1 knockdown demonstrated the converse effects on cell differentiation. ZIC1 misexpression was associated with altered Hedgehog signaling, and the Hedgehog antagonist cyclopamine reversed the osteo/adipogenic differentiation alterations associated with ZIC1 overexpression. Finally, human mesenchymal progenitor cells with or without ZIC1 overexpression were implanted in an ossicle assay in NOD-SCID gamma mice. ZIC1 overexpression led to significantly increased ossicle formation in comparison to the control, as assessed by radiographic and histologic measures. Together, these data suggest that ZIC1 represents a TF at the center of osteo/adipogenic cell fate determinations-findings that have relevance in the fields of stem cell biology and therapeutic regenerative medicine.
Topics: Animals; Mice; Humans; Adipogenesis; Hedgehog Proteins; Osteogenesis; Mice, Inbred NOD; Mice, SCID; Mesenchymal Stem Cells; Cell Differentiation; Transcription Factors
PubMed: 37317792
DOI: 10.1093/stmcls/sxad047 -
Tissue Engineering. Part B, Reviews Aug 2021Bone is a highly vascularized organ, providing structural support to the body, and its development, regeneration, and remodeling depend on the microvascular homeostasis.... (Review)
Review
Bone is a highly vascularized organ, providing structural support to the body, and its development, regeneration, and remodeling depend on the microvascular homeostasis. Loss or impairment of vascular function can develop diseases, such as large bone defects, avascular necrosis, osteoporosis, osteoarthritis, and osteopetrosis. In this review, we summarize how vasculature controls bone development and homeostasis in normal and disease cases. A better understanding of this process will facilitate the development of novel disease treatments that promote bone regeneration and remodeling. Specifically, approaches based on tissue engineering components, such as stem cells and growth factors, have demonstrated the capacity to induce bone microvasculature regeneration and mineralization. This knowledge will have relevant clinical implications for the treatment of bone disorders by developing novel pharmaceutical approaches and bone grafts. Finally, the tissue engineering approaches incorporating vascular components may widely be applied to treat other organ diseases by enhancing their regeneration capacity. Impact statement Bone vasculature is imperative in the process of bone development, regeneration, and remodeling. Alterations or disruption of the bone vasculature leads to loss of bone homeostasis and the development of bone diseases. In this study, we review the role of vasculature on bone diseases and how vascular tissue engineering strategies, with a detailed emphasis on the role of stem cells and growth factors, will contribute to bone therapeutics.
Topics: Bone Regeneration; Bone and Bones; Microvessels; Neovascularization, Physiologic; Osteogenesis
PubMed: 32940150
DOI: 10.1089/ten.TEB.2020.0154 -
International Journal of Molecular... Sep 2021Bone defects cause significant socio-economic costs worldwide, while the clinical "gold standard" of bone repair, the autologous bone graft, has limitations including... (Review)
Review
Bone defects cause significant socio-economic costs worldwide, while the clinical "gold standard" of bone repair, the autologous bone graft, has limitations including limited graft supply, secondary injury, chronic pain and infection. Therefore, to reduce surgical complexity and speed up bone healing, innovative therapies are needed. Bone tissue engineering (BTE), a new cross-disciplinary science arisen in the 21st century, creates artificial environments specially constructed to facilitate bone regeneration and growth. By combining stem cells, scaffolds and growth factors, BTE fabricates biological substitutes to restore the functions of injured bone. Although BTE has made many valuable achievements, there remain some unsolved challenges. In this review, the latest research and application of stem cells, scaffolds, and growth factors in BTE are summarized with the aim of providing references for the clinical application of BTE.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Bone and Bones; Humans; Osteogenesis; Stem Cells; Tissue Engineering; Tissue Scaffolds; Translational Research, Biomedical
PubMed: 34638571
DOI: 10.3390/ijms221910233 -
Rheumatology (Oxford, England) Mar 2020Enthesitis is a key manifestation of PsA and current knowledge supports the concept that it may be among the primary events in the development of this disease, as well... (Review)
Review
Enthesitis is a key manifestation of PsA and current knowledge supports the concept that it may be among the primary events in the development of this disease, as well as other forms of SpA. Patients with PsA seem to have a different threshold to mechanical stress, which may be genetically determined. Hence patients with psoriatic disease respond pathologically with inflammation after being exposed to physiological mechanical stress. Activation of pro-inflammatory mediators such as IL-17 and TNF-α as well as the influx of innate immune cells are key events in the development of enthesitis in PsA. Chronic entheseal inflammation is accompanied by new bone formation, leading to bony spurs in peripheral (entheseophytes) and axial (syndesmophytes) structures. This article reviews the current knowledge on the mechanisms involved in the development of enthesitis in patients with PsA.
Topics: Arthritis, Psoriatic; Enthesopathy; Humans; Inflammation; Interleukin-17; Interleukin-23; Osteogenesis; Stress, Mechanical; Tumor Necrosis Factor-alpha
PubMed: 32159793
DOI: 10.1093/rheumatology/keaa039 -
Bone May 2023FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this...
FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this study, we reported a novel mechanism of how bone development is regulated by FBXO11. FBXO11 gene knockdown by lentiviral transduction in mouse pre-osteoblast MC3T3-E1 cells leads to reduced osteogenic differentiation, while overexpressing FBXO11 accelerates their osteogenic differentiation in vitro. Furthermore, we generated two osteoblastic-specific FBXO11 conditional knockout mouse models, Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO mice. In both conditional FBXO11KO mouse models, we found FBXO11 deficiency inhibits normal bone growth, in which the osteogenic activity in FBXO11cKO mice is reduced, while osteoclastic activity is not significantly changed. Mechanistically, we found FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, leading to suppression of osteogenic activity and inhibition of bone matrix mineralization. FBXO11 knockdown in MC3T3-E1 cells reduced Snail1 protein ubiquitination and increased Snail1 protein accumulation in the cells, which eventually inhibited osteogenic differentiation. In conclusion, FBXO11 deficiency in osteoblasts inhibits bone formation through Snail1 accumulation, inhibiting osteogenic activity and bone mineralization.
Topics: Animals; Mice; Osteogenesis; Cell Differentiation; Calcification, Physiologic; Osteoclasts; Osteoblasts
PubMed: 36863499
DOI: 10.1016/j.bone.2023.116709 -
Cell Transplantation 2021In bone tissue engineering, tailored biomaterials mimicking mesenchymal stem cells (MSCs) niche could regulate cell behavior and fate decision. The mechanisms, however,... (Review)
Review
In bone tissue engineering, tailored biomaterials mimicking mesenchymal stem cells (MSCs) niche could regulate cell behavior and fate decision. The mechanisms, however, remain obscure. Recently, increasing evidence has shown that non-coding RNAs (ncRNAs) are critical modulators of the mechano-induced MSCs' responses. Mechanosensitive ncRNAs could convert various physical forces into biochemical signals, and orchestrate signaling networks that regulate the osteogenic differentiation of MSCs in their unique microenvironment. In this review, we focus on the mechanosensitive ncRNAs which could interpret mechanical stimuli during the osteogenesis of MSCs, summarize the signaling pathway networks by which these ncRNAs drive MSCs fate, and point out the limitations and the areas waiting for further exploration.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cells; Osteogenesis; RNA, Untranslated; Signal Transduction; Tissue Engineering
PubMed: 34628953
DOI: 10.1177/09636897211051382