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World Journal of Transplantation Sep 2021Voriconazole use has been associated with osteoarticular pain and periostitis, likely due to high fluoride content in the drug formulation. This phenomenon has been... (Review)
Review
Voriconazole use has been associated with osteoarticular pain and periostitis, likely due to high fluoride content in the drug formulation. This phenomenon has been described primarily with high dosage or prolonged course of voriconazole therapy in immunocompromised and transplant patient populations. Patients typically present with diffuse bony pains associated with elevated serum alkaline phosphatase and plasma fluoride levels in conjunction with radiographic findings suggestive of periostitis. We provide a comprehensive review of the literature to highlight salient characteristics commonly associated with voriconazole-induced periostitis.
PubMed: 34631468
DOI: 10.5500/wjt.v11.i9.356 -
CMAJ : Canadian Medical Association... Oct 2015
Topics: Aged; Antifungal Agents; Female; Humans; Periostitis; Radiography; Voriconazole
PubMed: 26032311
DOI: 10.1503/cmaj.141025 -
Proceedings of the National Academy of... Nov 2023We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist is due in part to impaired periosteal apposition. The...
We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive. Cathepsin K (Ctsk), together with additional stem cell surface markers, marks a subset of periosteal stem cells (PSCs) which possess self-renewal ability and inducible multipotency. is expressed in periosteal Ctsk-lineage cells, and global deletion decreases the pool of PSCs, impairs their clonal multipotency for differentiation into osteoblasts and chondrocytes and formation of bone organoids. Bulk RNA sequencing analysis of Ctsk-lineage PSCs demonstrated that deletion down-regulates signaling pathways associated with skeletal development, positive regulation of bone mineralization, and wound healing. Supporting these findings, deletion hampers the periosteal response to bone injury and impairs Ctsk-lineage periosteal cell recruitment. Ctsk-lineage PSCs express the PTH receptor and PTH treatment increases the % of PSCs, a response not seen in the absence of . Importantly, in the absence of , PTH-dependent increase in cortical thickness and periosteal bone formation is markedly impaired. Thus, this study provides insights into the regulation of a specific population of periosteal cells by a secreted local factor, and shows a central role for Sfrp4 in the regulation of Ctsk-lineage periosteal stem cell differentiation and function.
Topics: Mice; Animals; Cathepsin K; Stem Cell Niche; Osteogenesis; Periosteum; Cell Differentiation; Wnt Signaling Pathway; Proto-Oncogene Proteins
PubMed: 37931101
DOI: 10.1073/pnas.2312677120 -
Advanced Science (Weinheim,... Dec 2023Under diabetic conditions, blood glucose fluctuations and exacerbated immunopathological inflammatory environments pose significant challenges to periosteal regenerative...
Under diabetic conditions, blood glucose fluctuations and exacerbated immunopathological inflammatory environments pose significant challenges to periosteal regenerative repair strategies. Responsive immune regulation in damaged tissues is critical for the immune microenvironment, osteogenesis, and angiogenesis stabilization. Considering the high-glucose microenvironment of such acute injury sites, a functional glucose-responsive immunomodulation-assisted periosteal regeneration composite material-PLA(Polylactic Acid)/COLI(Collagen I)/Lipo(Liposome)-APY29 (PCLA)-is constructed. Aside from stimulating osteogenic differentiation, owing to the presence of surface self-assembled type I collagen in the scaffolds, PCLA can directly respond to focal area high-glucose microenvironments. The PCLA scaffolds trigger the release of APY29-loaded liposomes, shifting the macrophages toward the M2 phenotype, inhibiting the release of inflammatory cytokines, improving the bone immune microenvironment, and promoting osteogenic differentiation and angiogenesis. Bioinformatics analyses show that PCLA enhances bone repair by inhibiting the inflammatory signal pathway regulating the polarization direction and promoting osteogenic and angiogenic gene expression. In the calvarial periosteal defect model of diabetic rats, PCLA scaffolds induce M2 macrophage polarization and improve the inflammatory microenvironment, significantly accelerating periosteal repair. Overall, the PCLA scaffold material regulates immunity in fluctuating high-glucose inflammatory microenvironments, achieves relatively stable and favorable osteogenic microenvironments, and facilitates the effective design of functionalized biomaterials for bone regeneration therapy in patients with diabetes.
Topics: Rats; Humans; Animals; Osteogenesis; Periosteum; Tissue Scaffolds; Diabetes Mellitus, Experimental; Immunomodulation; Glucose
PubMed: 37973554
DOI: 10.1002/advs.202302874 -
Bone Feb 2021Diabetics are at increased risk for fracture, and experience severely impaired skeletal healing characterized by delayed union or nonunion of the bone. The periosteum...
Diabetics are at increased risk for fracture, and experience severely impaired skeletal healing characterized by delayed union or nonunion of the bone. The periosteum harbors osteochondral progenitors that can differentiate into chondrocytes and osteoblasts, and this connective tissue layer is required for efficient fracture healing. While bone marrow-derived stromal cells have been studied extensively in the context of diabetic skeletal repair and osteogenesis, the effect of diabetes on the periosteum and its ability to contribute to bone regeneration has not yet been explicitly evaluated. Within this study, we utilized an established murine model of type I diabetes to evaluate periosteal cell differentiation capacity, proliferation, and availability under the effect of a diabetic environment. Periosteal cells from diabetic mice were deficient in osteogenic differentiation ability in vitro, and diabetic mice had reduced periosteal populations of mesenchymal progenitors with a corresponding reduction in proliferation capacity following injury. Additionally, fracture callus mineralization and mature osteoblast activity during periosteum-mediated healing was impaired in diabetic mice compared to controls. We propose that the effect of diabetes on periosteal progenitors and their ability to aid in skeletal repair directly impairs fracture healing.
Topics: Animals; Bony Callus; Cell Differentiation; Diabetes Mellitus, Experimental; Fracture Healing; Mice; Osteogenesis; Periosteum
PubMed: 33221502
DOI: 10.1016/j.bone.2020.115764 -
Orthopaedic Surgery Sep 2022Repairing large segment bone defects is still a clinical challenge. Bone tissue prefabrication shows great translational potentials and has been gradually accepted... (Review)
Review
Repairing large segment bone defects is still a clinical challenge. Bone tissue prefabrication shows great translational potentials and has been gradually accepted clinically. Existing bone reconstruction strategies, including autologous periosteal graft, allogeneic periosteal transplantation, xenogeneic periosteal transplantation, and periosteal cell tissue engineering, are all clinically valuable treatments and have made significant progress in research. Herein, we reviewed the research progress of these techniques and briefly explained the relationship among in vivo microenvironment, mechanical force, and periosteum osteogenesis. Moreover, we also highlighted the importance of the critical role of periosteum in osteogenesis and explained current challenges and future perspective.
Topics: Autografts; Bioreactors; Humans; Osteogenesis; Periosteum; Tissue Engineering
PubMed: 35794789
DOI: 10.1111/os.13325 -
Frontiers in Physiology 2023The periosteum is a critical source of skeletal stem and progenitor cells (SSPCs) that form callus tissue in response to injury. There is yet to be a consensus on how to...
The periosteum is a critical source of skeletal stem and progenitor cells (SSPCs) that form callus tissue in response to injury. There is yet to be a consensus on how to identify SSPCs in the adult periosteum. The aim of this study was to understand how potential murine periosteal SSPC populations behave and in response to injury. We evaluated the differentiation potential of Sca1CD51 and Sca1CD51 cells following transplantation. , the Sca1CD51 population appears to be more primitive multipotent cells, but after transplantation, Sca1CD51 cells showed superior engraftment, expansion, and differentiation into chondrocytes and osteoblasts. Despite representing a clear population with flow cytometry, we identified very few Sca1CD51 cells histologically. Using a periosteal scratch injury model, we successfully mimicked the endochondral-like healing process seen in unstable fractures, including the expansion and osteochondral differentiation of αSMA cells following injury. CD51 cells were present in the cambium layer of resting periosteum and expanded following injury. Sca1CD51 cells were mainly localized in the outer periosteal layer. We found that injury increased colony-forming unit fibroblast (CFU-F) formation in the periosteum and led to rapid expansion of CD90 cells. Several other populations, including Sca1CD51 and CD34 cells, were expanded by day 7. Mice with enhanced fracture healing due to elevated Notch signaling mediated by NICD1 overexpression showed significant expansion of CD51 and CD34 cells in the early stages of healing, suggesting these populations contribute to more rapid healing. In conclusion, we demonstrate that periosteal injury leads to the expansion of various SSPC populations, but further studies are required to confirm their lineage hierarchy in the adult skeletal system. Our data indicate that CD51 skeletal progenitor cells are injury-responsive and show good engraftment and differentiation potential upon transplantation.
PubMed: 37731543
DOI: 10.3389/fphys.2023.1231352 -
Frontiers in Physiology 2016Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or... (Review)
Review
Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections.
PubMed: 27199772
DOI: 10.3389/fphys.2016.00157 -
Journal of Cellular Physiology May 2017Five to ten percent of fractures fail to heal normally leading to additional surgery, morbidity, and altered quality of life. Fracture healing involves the coordinated... (Review)
Review
Five to ten percent of fractures fail to heal normally leading to additional surgery, morbidity, and altered quality of life. Fracture healing involves the coordinated action of stem cells primarily coming from the periosteum which differentiate into the chondrocytes and osteoblasts, forming first the soft (cartilage) callus followed by the hard (bone) callus. These stem cells are accompanied by a vascular invasion that appears critical for the differentiation process and which may enable the entry of osteoclasts necessary for the remodeling of the callus into mature bone. However, more research is needed to clarify the signaling events that activate the osteochondroprogenitor cells of periosteum and stimulate their differentiation into chondrocytes and osteoblasts. Ultimately a thorough understanding of the mechanisms for differential regulation of these osteochondroprogenitors will aid in the treatment of bone healing and the prevention of delayed union and nonunion of fractures. In this review, evidence supporting the concept that the periosteal cells are the major cell sources of skeletal progenitors for the fracture callus will be discussed. The osteogenic differentiation of periosteal cells manipulated by Wnt/β-catenin, TGF/BMP, Ihh/PTHrP, and IGF-1/PI3K-Akt signaling in fracture repair will be examined. The effect of physical (hypoxia and hyperoxia) and chemical factors (reactive oxygen species) as well as the potential coordinated regulatory mechanisms in the periosteal progenitor cells promoting osteogenic differentiation will also be discussed. Understanding the regulation of periosteal osteochondroprogenitors during fracture healing could provide insight into possible therapeutic targets and thereby help to enhance future fracture healing and bone tissue engineering approaches. J. Cell. Physiol. 232: 913-921, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cell Differentiation; Fracture Healing; Humans; Models, Biological; Osteogenesis; Periosteum; Signal Transduction
PubMed: 27731505
DOI: 10.1002/jcp.25641 -
Scientific Reports Mar 2023Though triazole antifungals are the first choice for preventing and treating invasive fungal infections, periostitis caused by voriconazole has been described in...
Though triazole antifungals are the first choice for preventing and treating invasive fungal infections, periostitis caused by voriconazole has been described in emerging case reports; however, no studies exist on this association in real-world clinical settings. Our study aimed to identify the association between periostitis and triazole antifungals by analyzing data from the FDA Adverse Event Reporting System (FAERS). We extracted and analyzed reports on the association between periostitis and triazole antifungals in FAERS from the first quarter of 2004 to the second quarter of 2022 using OpenVigil 2.1. Disproportionality analysis was performed to evaluate the association between periostitis and triazole antifungals, and chi-squared (χ), relative reporting ratio (RRR), reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural networks (BCPNN) of information components (IC) were reported. In total, 143 patients experienced periostitis while using voriconazole. Disproportionality analysis identified an association between periostitis and voriconazole (χ = 82,689.0, RRR = 583.6, 95%CI [472.4, 721.1], PRR = 1808.9, 95%CI [1356.0, 2412.9], ROR = 1831.7, 95%CI [1371.6, 2446.3], IC = 9.2, 95%CI [8.6, 9.8]). However, no safety signals were observed between periostitis and other triazole antifungals. When stratified by sex and age, disproportionality analysis identified positive signals between periostitis and voriconazole. The possible association between periostitis and voriconazole should attract sufficient attention in clinical practice. Alternative treatment with other triazole antifungals can be considered, and causality needs to be verified in further prospective studies.
Topics: United States; Humans; Antifungal Agents; Voriconazole; Periostitis; Bayes Theorem; Prospective Studies; Adverse Drug Reaction Reporting Systems; United States Food and Drug Administration
PubMed: 36934109
DOI: 10.1038/s41598-023-27687-0