What makes an accurate and reliable subject-specific finite element model? A case study of an elephant femur

Journal of The Royal Society Interface, Год журнала: 2014, Номер 11(99), С. 20140854 - 20140854

Опубликована: Авг. 20, 2014

Simple Summary:The cartilage-to-bone transition is an essential process in healthy bone development and repair.Our previous work has shown that when the cells found within human periosteum (the membrane surrounding bone) are cultured serum (HS) as opposed to standard animal (FBS), these have greater bone-forming capacity assessed ectopic assay nude mice.What not understood molecular interactions permitted this enhanced biological potency.Herein, virtual networks created identify key proteins driving increased formation from cells.Key signalling factors were identified through a network analysis, where FGFR3 was pinpointed major differential regulator between grown HS FBS.This analysis validated of human-derived periosteal progenitor (PDCs) containing constitutively active (ca) FGFR3.Following removal we FGFR3-ca implanted on void filler scaffolds mice had abundance cartilage present compared scaffold normal/healthy cells.This suggests undergoing transitions protein may be potentially novel therapeutic target for diseases affected such during poor fracture healing.

Язык: Английский

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Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 4, 2024

Abstract Bone regeneration requires a well-orchestrated cellular and molecular response including robust vascularization recruitment of mesenchymal osteogenic cells. In femoral fractures, angiogenesis osteogenesis are closely coupled during the complex healing process. Here, we show with advanced longitudinal intravital multiphoton microscopy that early vascular sprouting is not directly to osteoprogenitor invasion calvarial bone regeneration. Early osteoprogenitors emerging from periosteum give rise bone-forming osteoblasts at injured edge. Microvessels growing inside lesions associated osteoprogenitors. Subsequently, cells collectively invade vascularized perfused lesion as multicellular layer, thereby advancing regenerative ossification. Vascular remodeling result in dynamic blood flow alterations accommodate bone. Single cell profiling bones demonstrates stromal heterogeneity comparable fractures increase types promoting Expression hypoxia-related genes slightly elevated reflecting ossification site. Endothelial Notch VEGF signaling alter growth repair without affecting progress. Our findings may have clinical implications for bioengineering approaches.

Язык: Английский

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Hyaluronan synthesis and degradation in cartilage and bone

Cellular and Molecular Life Sciences, Год журнала: 2007, Номер 65(3), С. 395 - 413

Опубликована: Окт. 26, 2007

Язык: Английский

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Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis, and bone mass

eLife, Год журнала: 2023, Номер 12

Опубликована: Фев. 13, 2023

M-CSF is a critical growth factor for myeloid lineage cells, including monocytes, macrophages, and osteoclasts. Tissue-resident macrophages in most organs rely on local M-CSF. However, it unclear what specific cells the bone marrow produce to maintain homeostasis. Here, we found that Adipoq-lineage progenitors but not mature adipocytes or peripheral adipose tissue, are major cellular source of M-CSF, with these producing at levels much higher than those produced by osteoblast cells. The high CSF1 expression also exist human marrow. Deficiency drastically reduces generation osteoclasts, leading severe osteopetrosis mice. Furthermore, osteoporosis ovariectomized mice can be significantly alleviated absence progenitors. Our findings identify as reveal their crucial contribution macrophage development, osteoclastogenesis, homeostasis, pathological loss.

Язык: Английский

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Leptin receptor+ cells promote bone marrow innervation and regeneration by synthesizing nerve growth factor

Nature Cell Biology, Год журнала: 2023, Номер 25(12), С. 1746 - 1757

Опубликована: Ноя. 27, 2023

The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this regulated. Here we found nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells required to maintain fibres in adult marrow. In nerveless marrow, steady-state haematopoiesis was normal and vascular were impaired myeloablation. LepR+ cells, the adipocytes they gave rise to, increased NGF production myeloablation, promoting sprouting regeneration. Nerves promoted activating β2 β3 adrenergic receptor signalling potentially adipocytes, increasing their of multiple factors. Peripheral thus through a reciprocal relationship which sustain synthesizing increase factors cells.

Язык: Английский

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Vitamin D and Bone: A Story of Endocrine and Auto/Paracrine Action in Osteoblasts

Nutrients, Год журнала: 2023, Номер 15(3), С. 480 - 480

Опубликована: Янв. 17, 2023

Despite its rigid structure, the bone is a dynamic organ, and highly regulated by endocrine factors. One of major regulatory hormones vitamin D. Its renal metabolite 1α,25-OH2D3 has both direct indirect effects on maintenance structure in health disease. In this review, we describe underlying processes that are directed bone-forming cells, osteoblasts. During formation process, osteoblasts undergo different stages which play central role signaling pathways activated via D receptor. Vitamin involved directing towards proliferation or apoptosis, regulates their differentiation to matrix producing controls subsequent mineralization matrix. The stage differentiation/mineralization important for effect gene transcription cellular response, many genes uniquely either before during mineralization. Moreover, contain complete machinery metabolize active ensure local effect. enzyme 1α-hydroxylase (CYP27B1) synthesizes functional osteoblasts, as well 24-hydroxylase (CYP24A1) degrades 1α,25-OH2D3. This shows past 100 years research, evolved from an regulator into autocrine/paracrine formation.

Язык: Английский

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Emerging roles of nerve‐bone axis in modulating skeletal system

Medicinal Research Reviews, Год журнала: 2024, Номер 44(4), С. 1867 - 1903

Опубликована: Фев. 29, 2024

Over the past decades, emerging evidence in literature has demonstrated that innervation of bone is a crucial modulator for skeletal physiology and pathophysiology. The nerve-bone axis sparked extensive preclinical clinical investigations aimed at elucidating contribution crosstalks to skeleton metabolism, homeostasis, injury repair through perspective neurobiology. To date, peripheral nerves have been widely reported mediate growth development fracture healing via secretion neurotransmitters, neuropeptides, axon guidance factors, neurotrophins. Relevant studies further identified several critical neural pathways stimulate profound alterations cell biology, revealing complex interplay between nerve systems. In addition, inspired by crosstalk, novel drug delivery systems bioactive materials developed emulate facilitate process natural neuromodulation, eventually boosting osteogenesis ideal tissue regeneration. Overall, this work aims review research findings contribute deepening current understanding axis, bringing forth some schemas can be translated into scenario highlight roles neuromodulation system.

Язык: Английский

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Fibrous periosteum repairs bone fracture and maintains the healed bone throughout mouse adulthood

Developmental Cell, Год журнала: 2024, Номер 59(9), С. 1192 - 1209.e6

Опубликована: Март 29, 2024

Bone is regarded as one of few tissues that heals without fibrous scar. The outer layer the periosteum covered with tissue, whose function in bone formation unknown. We herein developed a system to distinguish fate fibrous-layer periosteal cells (FL-PCs) from skeletal stem/progenitor (SSPCs) cambium-layer and marrow mice. showed FL-PCs did not participate steady-state osteogenesis, but formed main body fibrocartilaginous callus during fracture healing. Moreover, invaded after fracture, forming neo-SSPCs continued maintain healed bones throughout adulthood. FL-PC-derived expressed lower levels osteogenic signature genes displayed differentiation activity than preexisting SSPCs. Consistent this, were thinner more slowly normal bones. Thus, becomes cellular origin alters properties permanently.

Язык: Английский

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Skeletal stem and progenitor cells in bone development and repair

Journal of Bone and Mineral Research, Год журнала: 2024, Номер unknown

Опубликована: Апрель 30, 2024

Abstract Bone development, growth, and repair are complex processes involving various cell types interactions, with central roles played by skeletal stem progenitor cells. Recent research brought new insights into the precursor populations that mediate intramembranous endochondral bone development. Later in life, many of cellular molecular mechanisms determining development reactivated upon fracture, powerful trauma-induced signaling cues triggering a variety postnatal stem/progenitor cells (SSPCs) residing near defect. Interestingly, this injury context, current evidence suggests fates both SSPCs differentiated can be considerably flexible dynamic, multiple sources activated to operate as functional progenitors generating chondrocytes and/or osteoblasts. The combined implementation vivo lineage tracing, surface marker-based selection, single-cell analyses, high-resolution situ imaging has strongly improved our diversity developmental reparative subsets, while also unveiling complexity their dynamics, hierarchies, relationships. Albeit incompletely understood at present, findings supporting flexibility possibly plasticity among osteogenic challenge classical dogma single primitive, self-renewing, multipotent driving tissue formation regeneration from apex hierarchical strictly unidirectional differentiation tree. We here review state field newest discoveries origin, identity, during discuss contributions adult SSPC fracture repair, reflect on dynamism relationships precursors lineages. Further directed unraveling heterogeneity capacities SSPCs, well regulatory fate functioning, will offer vital options for clinical translation toward compromised healing regenerative medicine.

Язык: Английский

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Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Янв. 25, 2024

Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes SSPC remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during which triggers and impairs fracture healing. Local injection human rGCA young mice induced delayed repair. Genetic deletion Gca monocytes/macrophages was sufficient to rejuvenate repair aged alleviate senescence. Mechanistically, GCA binds plexin-B2 receptor activates Arg2-mediated mitochondrial dysfunction, resulting cellular Depletion Plxnb2 SSPCs impaired Administration GCA-neutralizing antibody enhanced healing mice. Thus, our study senescent within trigger secondary senescence, neutralization represents promising therapy for nonunion or union elderly individuals.

Язык: Английский

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