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NanoZnO-modified titanium implants for enhanced anti-bacterial activity, osteogenesis and corrosion resistance.
Wang, Z, Wang, X, Wang, Y, Zhu, Y, Liu, X, Zhou, Q
Journal of nanobiotechnology. 2021;(1):353
Abstract
Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed.
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The Human Gut Microbiota: A Key Mediator of Osteoporosis and Osteogenesis.
Seely, KD, Kotelko, CA, Douglas, H, Bealer, B, Brooks, AE
International journal of molecular sciences. 2021;(17)
Abstract
An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.
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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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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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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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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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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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Osteocyte Mechanobiology.
Uda, Y, Azab, E, Sun, N, Shi, C, Pajevic, PD
Current osteoporosis reports. 2017;(4):318-325
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PURPOSE OF REVIEW Over the past decades, osteocytes have emerged as mechano-sensors of bone and master regulators of bone homeostasis. This article summarizes latest research and progress made in understanding osteocyte mechanobiology and critically reviews tools currently available to study these cells. RECENT FINDINGS Whereas increased mechanical forces promote bone formation, decrease loading is always associated with bone loss and skeletal fragility. Recent studies identified cilia, integrins, calcium channels, and G-protein coupled receptors as important sensors of mechanical forces and Ca2+ and cAMP signaling as key effectors. Among transcripts regulated by mechanical forces, sclerostin and RANKL have emerged as potential therapeutic targets for disuse-induced bone loss. In this paper, we review the mechanisms by which osteocytes perceive and transduce mechanical cues and the models available to study mechano-transduction. Future directions of the field are also discussed.