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Biological Factors, Metals, and Biomaterials Regulating Osteogenesis through Autophagy.
di Giacomo, V, Cataldi, A, Sancilio, S
International journal of molecular sciences. 2020;(8)
Abstract
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. This review provides a revision of the literature on all the exogen factors that can modulate osteogenesis through autophagy regulation. Metal ion exposition, mechanical stimuli, and biological factors, including hormones, nutrients, and metabolic conditions, were taken into consideration for their ability to tune osteogenic differentiation through autophagy. In addition, an exhaustive overview of biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is provided as well. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for finely tailoring innovative therapeutic treatments and designing novel biomaterials.
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Phytochemicals impact on osteogenic differentiation of mesenchymal stem cells.
Sharifi, S, Moghaddam, FA, Abedi, A, Maleki Dizaj, S, Ahmadian, S, Abdolahinia, ED, Khatibi, SMH, Samiei, M
BioFactors (Oxford, England). 2020;(6):874-893
Abstract
Medicinal plants have always been utilized for the prevention and treatment of the spread of different diseases all around the world. To name some traditional medicine that has been used over centuries, we can refer to phytochemicals such as naringin, icariin, genistein, and resveratrol gained from plants. Osteogenic differentiation and mineralization of stem cells can be the result of specific bioactive compounds from plants. One of the most appealing choices for therapy can be mesenchymal stem cells (MSCs) because it has a great capability of self-renewal and differentiation into three descendants, namely, endoderm, mesoderm, and ectoderm. Stem cell gives us the glad tidings of great advances in tissue regeneration and transplantation field for treatment of diseases. Using plant bioactive phytochemicals also holds tremendous promises in treating diseases such as osteoporosis. The purpose of the present review article thus is to investigate what are the roles and consequences of phytochemicals on osteogenic differentiation of MSCs.
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3.
The Actions of IGF-1 in the Growth Plate and Its Role in Postnatal Bone Elongation.
Racine, HL, Serrat, MA
Current osteoporosis reports. 2020;(3):210-227
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Abstract
PURPOSE OF REVIEW Bone elongation is a complex process driven by multiple intrinsic (hormones, growth factors) and extrinsic (nutrition, environment) variables. Bones grow in length by endochondral ossification in cartilaginous growth plates at ends of developing long bones. This review provides an updated overview of the important factors that influence this process. RECENT FINDINGS Insulin-like growth factor-1 (IGF-1) is the major hormone required for growth and a drug for treating pediatric skeletal disorders. Temperature is an underrecognized environmental variable that also impacts linear growth. This paper reviews the current state of knowledge regarding the interaction of IGF-1 and environmental factors on bone elongation. Understanding how internal and external variables regulate bone lengthening is essential for developing and improving treatments for an array of bone elongation disorders. Future studies may benefit from understanding how these unique relationships could offer realistic new approaches for increasing bone length in different growth-limiting conditions.
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The Osteoporosis/Microbiota Linkage: The Role of miRNA.
De Martinis, M, Ginaldi, L, Allegra, A, Sirufo, MM, Pioggia, G, Tonacci, A, Gangemi, S
International journal of molecular sciences. 2020;(23)
Abstract
Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.
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The emerging role of extracellular Ca2+ in osteo/odontogenic differentiation and the involvement of intracellular Ca 2+ signaling: From osteoblastic cells to dental pulp cells and odontoblasts.
An, S
Journal of cellular physiology. 2019;(3):2169-2193
Abstract
Calcium ions (Ca2+ ) is the main element of dental pulp capping materials. Ca 2+ signaling plays a crucial role in a myriad of cell activities. An overwhelming array of studies have already reported the experimental and clinical benefits of Ca2+ -enriched materials in the treatment of teeth with accidental vital pulp exposure and incomplete root formation. Thus, Ca2+ signaling has always been an excellent target for the design of various novel biomaterials for use in revitalizing or regenerative endodontic procedures. However, the molecular mechanisms that enable dental pulp cells (DPCs) to detect and respond to extracellular Ca2+ have not been characterized in detail before. In this review, we mainly outline the pathways by which the cell detects and responds to extracellular Ca2+ , as well as the relevant regulatory paths in DPCs and odontoblasts, and discuss the potential role of Ca2+ as a therapeutic tool. Moreover, because DPCs share many of the same functional properties that are found in osteoblasts, some comparisons with bone cells were additionally incorporated into this text.
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Biological Properties of Calcium Phosphate Bioactive Glass Composite Bone Substitutes: Current Experimental Evidence.
Karadjian, M, Essers, C, Tsitlakidis, S, Reible, B, Moghaddam, A, Boccaccini, AR, Westhauser, F
International journal of molecular sciences. 2019;(2)
Abstract
Standard treatment for bone defects is the biological reconstruction using autologous bone-a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.
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The Emerging Role of Glucose Metabolism in Cartilage Development.
Hollander, JM, Zeng, L
Current osteoporosis reports. 2019;(2):59-69
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Abstract
PURPOSE OF REVIEW Proper cartilage development is critical to bone formation during endochondral ossification. This review highlights the current understanding of various aspects of glucose metabolism in chondrocytes during cartilage development. RECENT FINDINGS Recent studies indicate that chondrocytes transdifferentiate into osteoblasts and bone marrow stromal cells during endochondral ossification. In cartilage development, signaling molecules, including IGF2 and BMP2, tightly control glucose uptake and utilization in a stage-specific manner. Perturbation of glucose metabolism alters the course of chondrocyte maturation, suggesting a key role for glucose metabolism during endochondral ossification. During prenatal and postnatal growth, chondrocytes experience bursts of nutrient availability and energy expenditure, which demand sophisticated control of the glucose-dependent processes of cartilage matrix production, cell proliferation, and hypertrophy. Investigating the regulation of glucose metabolism may therefore lead to a unifying mechanism for signaling events in cartilage development and provide insight into causes of skeletal growth abnormalities.
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Osteoporosis in primary biliary cholangitis.
Danford, CJ, Trivedi, HD, Papamichael, K, Tapper, EB, Bonder, A
World journal of gastroenterology. 2018;(31):3513-3520
Abstract
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to significant morbidity in this population, yet evidence for effective therapy is lacking. We sought to summarize our current understanding of the pathophysiology of osteoporosis in PBC, as well as current and emerging therapies in order to guide future research directions. A complete search with a comprehensive literature review was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, and the Countway Library. Osteoporosis in PBC is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Despite this fundamental difference, current treatment recommendations are based primarily on experience with postmenopausal osteoporosis. Trials specific to PBC-related osteoporosis are small and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in PBC relies on the mitigation of risk factors such as smoking and alcohol use, as well as encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in PBC and summarizes current and emerging therapies.
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9.
Transcriptional Mechanisms of Secondary Fracture Healing.
Roberts, JL, Paglia, DN, Drissi, H
Current osteoporosis reports. 2018;(2):146-154
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PURPOSE OF REVIEW Growing evidence supports the critical role of transcriptional mechanisms in promoting the spatial and temporal progression of bone healing. In this review, we evaluate and discuss new transcriptional and post-transcriptional regulatory mechanisms of secondary bone repair, along with emerging evidence for epigenetic regulation of fracture healing. RECENT FINDINGS Using the candidate gene approach has identified new roles for several transcription factors in mediating the reactive, reparative, and remodeling phases of fracture repair. Further characterization of the different epigenetic controls of fracture healing and fracture-driven transcriptome changes between young and aged fracture has identified key biological pathways that may yield therapeutic targets. Furthermore, exogenously delivered microRNA to post-transcriptionally control gene expression is quickly becoming an area with great therapeutic potential. Activation of specific transcriptional networks can promote the proper progression of secondary bone healing. Targeting these key factors using small molecules or through microRNA may yield effective therapies to enhance and possibly accelerate fracture healing.
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A Perspective on Stem Cells as Biological Systems that Produce Differentiated Osteoblasts and Odontoblasts.
Ariffin, SH, Manogaran, T, Abidin, IZ, Wahab, RM, Senafi, S
Current stem cell research & therapy. 2017;(3):247-259
Abstract
Stem cells (SCs) are capable of self-renewal and multilineage differentiation. Human mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) which can be obtained from multiple sources, are suitable for application in regenerative medicine and transplant therapy. The aim of this review is to evaluate the potential of genomic and proteomic profiling analysis to identify the differentiation of MSCs and HSCs towards osteoblast and odontoblast lineages. In vitro differentiation towards both of these lineages can be induced using similar differentiation factors. Gene profiling cannot be utilised to confirm the lineages of these two types of differentiated cells. Differentiated cells of both lineages express most of the same markers. Most researchers have detected the expression of genes such as ALP, OCN, OPN, BMP2 and RUNX2 in osteoblasts and the expression of the DSPP gene in odontoblasts. Based on their cell-type specific protein profiles, various proteins are differentially expressed by osteoblasts and odontoblasts, except for vimentin and heterogeneous nuclear ribonucleoprotein C, which are expressed in both cell types, and LOXL2 protein, which is expressed only in odontoblasts.