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Cell Stem Cell Nov 2022A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We...
A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We found that SSCs in adult bone marrow can be identified based on Lepr and Adiponectin-cre/creER expression while SSCs in adult periosteum can be identified based on Gli1 expression. Under steady-state conditions, new bone arose primarily from bone marrow SSCs. After bone injuries, both SSC populations began proliferating but made very different contributions to bone repair. Drill injuries were primarily repaired by LepR/Adiponectin bone marrow SSCs. Conversely, bicortical fractures were primarily repaired by Gli1 periosteal SSCs, though LepR/Adiponectin bone marrow cells transiently formed trabecular bone at the fracture site. Gli1 periosteal cells also regenerated LepR bone marrow stromal cells that expressed hematopoietic niche factors at fracture sites. Different bone injuries are thus repaired by different SSCs, with periosteal cells regenerating bone and marrow stroma after non-stabilized fractures.
Topics: Humans; Adult; Bone Marrow; Zinc Finger Protein GLI1; Adiponectin; Stem Cells; Periosteum; Bone Marrow Cells
PubMed: 36272401
DOI: 10.1016/j.stem.2022.10.002 -
Advanced Science (Weinheim,... Jan 2022Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism...
Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism is poorly understood. Here, it is shown that myeloid-lineage cells differentiate into subgroups and regulate periosteal bone formation in response to mechanical loading. Mechanical loading on tibiae significantly increases the number of periosteal myeloid-lineage cells and the levels of active transforming growth factor β (TGF-β), resulting in cortical bone formation. Knockout of Tgfb1 in myeloid-lineage cells attenuates mechanical loading-induced periosteal bone formation in mice. Moreover, CD68 F4/80 macrophages, a subtype of myeloid-lineage cells, express and activate TGF-β1 for recruitment of osteoprogenitors. Particularly, mechanical loading induces the differentiation of periosteal CD68 F4/80 myeloid-lineage cells to the CD68 F4/80 macrophages via signaling of piezo-type mechanosensitive ion channel component 1 (Piezo1) for TGF-β1 secretion. Importantly, CD68 F4/80 macrophages activate TGF-β1 by expression and secretion of thrombospondin-1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading-induced TGF-β activation and recruitment of osteoprogenitors in the periosteum. The results suggest that periosteal myeloid-lineage cells respond to mechanical forces and consequently produce and activate TGF-β1 for periosteal bone formation.
Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; B7-1 Antigen; Cortical Bone; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; Osteogenesis; Periosteum; Signal Transduction; Transforming Growth Factor beta1
PubMed: 34854257
DOI: 10.1002/advs.202103343 -
AACE Clinical Case Reports 2022Voriconazole treatment has been associated with diffuse periostitis, especially in immunocompromised patients who have had transplants or are on immunosuppressants....
BACKGROUND/OBJECTIVE
Voriconazole treatment has been associated with diffuse periostitis, especially in immunocompromised patients who have had transplants or are on immunosuppressants. Here, we present a case of diffuse periostitis induced by prophylactic low-dose voriconazole for pulmonary aspergillosis.
CASE REPORT
A 66-year-old woman presented with 1 year of progressive, diffuse bone pain most prominent over the left shoulder and bilateral hips. She had a history of sarcoidosis requiring a single orthotopic lung transplant. Left phalangeal soft tissue swelling and painful nodules without clubbing were noted on examination. Prophylactic voriconazole 200 mg twice a day for pulmonary aspergillosis was prescribed for over 7 years. Elevated levels of alkaline phosphatase (469 units/L [reference range, 38-126]), bone-specific alkaline phosphatase (125 μg/L [0-20]), and parathyroid hormone (137 pg/mL [8-54]) and normal c-telopeptide level (842 pg/mL [34-1037]) were noted. Radiographs showed "multifocal periostitis" in both hip joints and bilateral proximal femurs, findings suggestive of voriconazole-induced periostitis deformans. Voriconazole was discontinued, and the patient improved symptomatically, despite persistent bone deformities on imaging.
DISCUSSION
Diffuse bone pain can be due to various pathologies, including metabolic or inflammatory diseases and bone tumors. Voriconazole-induced periostitis is caused by skeletal fluorosis, which can result in diffuse bone pain. It is a clinical diagnosis that is supported with radiologic findings, including focal, nodular, dense, and irregular periosteal reactions. Biochemical evaluation may reveal elevated alkaline phosphatase levels, but it is usually related to normal voriconazole trough levels. Periostitis is a benign condition, and discontinuation of the drug usually leads to clinical improvement.
CONCLUSION
Voriconazole-induced periostitis should be considered as a diagnosis in elderly, immunosuppressed patients with diffuse bone pain on antifungal treatment. Early recognition of voriconazole-induced periostitis may result in both improved patient clinical outcomes and avoidance of unnecessary diagnostic testing.
PubMed: 36189133
DOI: 10.1016/j.aace.2022.05.001 -
Polish Journal of Radiology 2022Magnetic resonance imaging (MRI) is a powerful imaging modality in the evaluation of musculoskeletal (MSK) soft tissue, joint, and bone infections. It allows prompt... (Review)
Review
Magnetic resonance imaging (MRI) is a powerful imaging modality in the evaluation of musculoskeletal (MSK) soft tissue, joint, and bone infections. It allows prompt diagnosis and assessment of the extent of disease, which permits timely treatment to optimize long-term clinical outcomes. MRI is highly sensitive and specific in detecting the common findings of MSK infections, such as superficial and deep soft tissue oedema, joint, bursal and tendon sheath effusions, lymphadenopathy, bone marrow oedema, erosive bone changes and periostitis, and bone and cartilage destruction and sequestration. Contrast-enhanced MRI allows detection of non-enhancing fluid collections and necrotic tissues, rim-enhancing abscesses, heterogeneously or diffusely enhancing phlegmons, and enhancing active synovitis. Diffusion-weighted imaging (DWI) is useful in detecting soft-tissue abscesses, particularly in patients who cannot receive gadolinium-based intravenous contrast. MRI is less sensitive than computed tomography (CT) in detecting soft-tissue gas. This article describes the pathophysiology of pyogenic MSK infections, including the route of contamination and common causative organisms, typical MR imaging findings of various soft tissue infections including cellulitis, superficial and deep fasciitis and necrotizing fasciitis, pyomyositis, infectious bursitis, infectious tenosynovitis, and infectious lymphadenitis, and of joint and bone infections including septic arthritis and osteomyelitis (acute, subacute, and chronic). The authors also discuss MRI findings and pitfalls related to infected hardware and diabetic foot infections, and briefly review standards of treatment of various pyogenic MSK infections.
PubMed: 35505859
DOI: 10.5114/pjr.2022.113825