Fibrous Dysplasia in a 120,000+ Year Old Neandertal from Krapina, Croatia

Monge, Janet; Kricun, Morrie E.; Radovčić, Jakov; Radovčić, Davorka; Mann, Alan; Frayer, David W.

doi:10.1371/journal.pone.0064539

Cited by 31 publications

(15 citation statements)

References 16 publications

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“…FD is an ancient disease that can be found in Neanderthal bone [64] and presents with pain, skeletal deformity and pathologic fractures. On radiographs, ground glass lesions and endosteal scalloping are observed [65].…”

Section: Beyond Resorption: Regulation Of the Bone Remodeling Cycle Imentioning

confidence: 99%

Osteoclasts: more than ‘bone eaters’

Charles

Aliprantis

2014

Trends in Molecular Medicine

325

250

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As the only cells definitively shown to degrade bone, osteoclasts are key mediators of skeletal diseases including osteoporosis. Bone forming osteoblasts, and hematopoietic and immune system cells, each influence osteoclast formation and function, but the reciprocal impact of osteoclasts on these cells is less well appreciated. Here, we highlight functions osteoclasts perform beyond bone resorption. First, we consider how osteoclast signals may contribute to bone formation by osteoblasts and the pathology of bone lesions, such as fibrous dysplasia and giant cell tumors. Second, we review the interaction of osteoclasts with the hematopoietic system, including the stem cell niche and adaptive immune cells. Connections between osteoclasts and other cells in the bone microenvironment are discussed within a clinically relevant framework. Keywordsosteoclast; osteoblast; bone remodeling; osteopetrosis; osteoporosis; PTH Bone remodeling and osteoclasts 101Bone is a composite tissue of protein and mineral, which undergoes continual remodeling to grow, heal damage, and regulate calcium and phosphate metabolism. This remodeling process is executed by the concerted and sequential effort of bone resorbing osteoclasts and bone forming osteoblasts, acting in what has been termed the basic multicellular unit (BMU) ( Figure 1A). Osteocytes, long-lived osteoblast-derived cells that reside within the bone matrix, monitor bone quality and stress, and coordinate remodeling through membrane bound and secreted factors. Skeletal integrity is maintained throughout the lifespan by matching bone formation and resorption, a process referred to as osteoclast:osteoblast 'coupling.' Coupling is thoroughly summarized in recent excellent reviews [1,2] and in Figure 1.Osteoclasts are multinucleated giant cells that differentiate from myeloid precursors under the influence of the cytokines macrophage colony stimulating factor (MCSF) and receptor © 2014 Elsevier Ltd. All rights reserved.Corresponding Author: Antonios O. Aliprantis, M.D., Ph.D., (AALIPRANTIS@PARTNERS.ORG). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript activator of NF-κB ligand (RANKL) supplied by osteoblasts and/or osteocytes ( Figure 1A) [3]. A decoy receptor for RANKL called osteoprotegrin (OPG), which is also made by the osteoblast lineage, tempers osteoclast differentiation [4]. Osteoclasts degrade bone by the polarized secretion of proteolytic enzymes (e.g. cathepsin K) and acid, which hydrolyze and solubilize the organic and inorganic...

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Section: Beyond Resorption: Regulation Of the Bone Remodeling Cycle Imentioning

confidence: 99%

Osteoclasts: more than ‘bone eaters’

Charles

Aliprantis

2014

Trends in Molecular Medicine

325

250

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“…Nearly all palaeopathological examples of cancer only dates to the past 500 years of human history, and evidence for cancer before the modern era is indeed rare (Binder, Roberts, Spencer, Antoine, & Cartwright, ). Early confirmation of neoplastic disease is however indicated by a lesion on an archaic Homo mandible from Kanam, Kenya (Phelan et al., ), and a fibrous dysplasia on a Neanderthal rib dated to 120 ka from the site of Krapina, Croatia (Monge et al., ). The recent discovery of neoplastic tumours in members of Australopithecus and early Homo (Odes et al., ; Randolph‐Quinney et al., ) dated to 1.98 and c .…”

Section: Ancient Human Health and Oncogenesismentioning

confidence: 99%

“…Chronological incidence of prehistoric oncogenic tumours and important milestones concerning cancer aetiology and treatment (Binder et al., ; Bona et al., ; Monge et al., ; Odes et al., ; Phelan et al., ; Randolph‐Quinney et al., ) (‘Rom.’ and ‘Med.’ referes to Roman and Medieval Periods, respectively).…”

Section: Ancient Human Health and Oncogenesismentioning

confidence: 99%

Ancient oncogenesis, infection and human evolution

Rifkin

Potgieter

Ramond

et al. 2017

Evolutionary Applications

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The recent discovery that malignant neoplastic lesions date back nearly 2 million years ago not only highlights the antiquity of cancer in the human lineage, but also provides remarkable insight into ancestral hominin disease pathology. Using these Early Pleistocene examples as a point of departure, we emphasize the prominent role of viral and bacterial pathogens in oncogenesis and evaluate the impact of pathogens on human evolutionary processes in Africa. In the Shakespearean vernacular “what's past is prologue,” we highlight the significance of novel information derived from ancient pathogenic DNA. In particular, and given the temporal depth of human occupation in sub‐Saharan Africa, it is emphasized that the region is ideally positioned to play a strategic role in the discovery of ancient pathogenic drivers of not only human mortality, but also human evolution. Ancient African pathogen genome data can provide novel revelations concerning human‐pathogen coevolutionary processes, and such knowledge is essential for forecasting the ways in which emerging zoonotic and increasingly transmissible diseases might influence human demography and longevity in the future.

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“…V průběhu evoluce se totiž imunitní systém neměl příliš šanci s nádory potkat. Přestože jsou v archeologických výzkumech popisovány nálezy kostí neandrtálců deformovaných nádory [1], naprostá většina malignit se v současné době objevuje až po 50. roce života (graf 1), přičemž historická data ukazují, že ještě v polovině 19. století byla očekávaná doba přežití ve Velké Británii jen 25-30 let [2]. S jistou formou nadsázky lze tedy tvrdit, že imunitní systém člověka se s nádory "potkává" teprve posledních 150 let, kdy došlo k významnému prodloužení průměrné doby přežití, a tím k vyššímu výskytu nádorových onemocnění.…”

Section: úVodunclassified

Escape Strategies of Tumors from Immune Surveillence

Šťastný¹,

Řı́hová²

2015

Klin Onkol

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Imunitní systém musí být na jedné straně schopen efektivně zasáhnout proti cizím a nebezpečným patogenům, na straně druhé musí být schopen rozpoznat a tolerovat naše vlastní tkáně a orgány. Aktivita imunitního systému je ovlivňována celou řadou pozitivních (stimulačních) a negativních (inhibičních) signálů. Ně kte ré z těchto inhibičních receptorů zabraňují poškození našich tkání v místě zánětu tím, že tlumí příliš silnou či dlouhou imunitní reakci. Plní tak fyziologickou ochrannou funkci před silnou zánětlivou reakcí a možnou autoimunitní patologií. Ně kte ré z těchto mechanizmů jsou ovšem využívány nádory k tomu, aby unikly pozornosti imunitního systému. Další únikové strategie spočívají v produkci cytokinů a faktorů vytvářejících v nádorovém mikroprostředí silnou imunosupresi, která zabraňuje efektivní imunitní odpovědi. Tato práce si klade za cíl popsat nejčastější strategie, které jsou nádory využívány k potlačení imunitní reakce. Klíčová slova imunitní úniky-únikové mechanizmy nádorů-imunoterapie-CTLA-4-PD-1-kontrolní body imunitní reakce Summary Immune system must be able to protect us from foreign dangerous pathogens, but on the other side, it must be able to recognize our own tissues and organs. Activity of the immune system is aff ected by many positive (stimulatory) and negative (inhibitory) signals. Some of these negative receptors protect us from damage of our tissues at a place of infl ammation as it blocks too intensive or long-lasting immune reaction. Thereby, they have a physiological protective function against strong infl ammatory reaction and possible subsequent autoimmune pathology. However, some of these mechanisms are also utilized by tumors to avoid immune recognition and attention of the immune cells. Other tumor escape mechanisms involve increased production of cytokines and factors which are responsible for immunosuppressive tumor microenvironment where eff ective immune response is actively blocked. This review summarizes the most frequently used strategies, which are utilized by tumors to avoid immune recognition and/ or killing by the immune cells.

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Fibrous Dysplasia in a 120,000+ Year Old Neandertal from Krapina, Croatia

Cited by 31 publications

References 16 publications

Osteoclasts: more than ‘bone eaters’

Osteoclasts: more than ‘bone eaters’

Ancient oncogenesis, infection and human evolution

Escape Strategies of Tumors from Immune Surveillence

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