Abstract:
:Osteoclasts are multinucleated giant cells that resorb bone, ensuring development and continuous remodelling of the skeleton and the bone marrow haematopoietic niche. Defective osteoclast activity leads to osteopetrosis and bone marrow failure1-9, whereas excess activity can contribute to bone loss and osteoporosis10. Osteopetrosis can be partially treated by bone marrow transplantation in humans and mice11-18, consistent with a haematopoietic origin of osteoclasts13,16,19 and studies that suggest that they develop by fusion of monocytic precursors derived from haematopoietic stem cells in the presence of CSF1 and RANK ligand1,20. However, the developmental origin and lifespan of osteoclasts, and the mechanisms that ensure maintenance of osteoclast function throughout life in vivo remain largely unexplored. Here we report that osteoclasts that colonize fetal ossification centres originate from embryonic erythro-myeloid progenitors21,22. These erythro-myeloid progenitor-derived osteoclasts are required for normal bone development and tooth eruption. Yet, timely transfusion of haematopoietic-stem-cell-derived monocytic cells in newborn mice is sufficient to rescue bone development in early-onset autosomal recessive osteopetrosis. We also found that the postnatal maintenance of osteoclasts, bone mass and the bone marrow cavity involve iterative fusion of circulating blood monocytic cells with long-lived osteoclast syncytia. As a consequence, parabiosis or transfusion of monocytic cells results in long-term gene transfer in osteoclasts in the absence of haematopoietic-stem-cell chimerism, and can rescue an adult-onset osteopetrotic phenotype caused by cathepsin K deficiency23,24. In sum, our results identify the developmental origin of osteoclasts and a mechanism that controls their maintenance in bones after birth. These data suggest strategies to rescue osteoclast deficiency in osteopetrosis and to modulate osteoclast activity in vivo.
journal_name
Naturejournal_title
Natureauthors
Jacome-Galarza CE,Percin GI,Muller JT,Mass E,Lazarov T,Eitler J,Rauner M,Yadav VK,Crozet L,Bohm M,Loyher PL,Karsenty G,Waskow C,Geissmann Fdoi
10.1038/s41586-019-1105-7subject
Has Abstractpub_date
2019-04-01 00:00:00pages
541-545issue
7753eissn
0028-0836issn
1476-4687pii
10.1038/s41586-019-1105-7journal_volume
568pub_type
杂志文章相关文献
NATURE文献大全abstract::Memory is believed to depend on activity-dependent changes in the strength of synapses. In part, this view is based on evidence that the efficacy of synapses can be enhanced or depressed depending on the timing of pre- and postsynaptic activity. However, when such plastic synapses are incorporated into neural network ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01530
更新日期:2003-04-03 00:00:00
abstract::Magnetic compass information has a key role in bird orientation, but the physiological mechanisms enabling birds to sense the Earth's magnetic field remain one of the unresolved mysteries in biology. Two biophysical mechanisms have become established as the most promising magnetodetection candidates. The iron-mineral-...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08528
更新日期:2009-10-29 00:00:00
abstract::Many collective human activities, including violence, have been shown to exhibit universal patterns. The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions. However, the possibility of universal patterns r...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08631
更新日期:2009-12-17 00:00:00
abstract::Many eukaryotic cellular and viral proteins have a covalently attached myristoyl group at the amino terminus. One such protein is recoverin, a calcium sensor in retinal rod cells, which controls the lifetime of photoexcited rhodopsin by inhibiting rhodopsin kinase. Recoverin has a relative molecular mass of 23,000 (M[...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/38310
更新日期:1997-09-11 00:00:00
abstract::Crustal faults have long been identified as sites where localized sliding motion occurs during earthquakes, which allows for the relative motion between adjacent crustal blocks. Although there is a growing awareness that we must understand the evolution of fault systems on many timescales to relate present-day crustal...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01354
更新日期:2003-01-30 00:00:00
abstract::Signal sequences target proteins for secretion from cells or for integration into cell membranes. As nascent proteins emerge from the ribosome, signal sequences are recognized by the signal recognition particle (SRP), which subsequently associates with its receptor (SR). In this complex, the SRP and SR stimulate each ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02250
更新日期:2004-01-15 00:00:00
abstract::Peptidoglycan (PG), an essential structure in the cell walls of the vast majority of bacteria, is critical for division and maintaining cell shape and hydrostatic pressure. Bacteria comprising the Chlamydiales were thought to be one of the few exceptions. Chlamydia harbour genes for PG biosynthesis and exhibit suscept...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12892
更新日期:2014-02-27 00:00:00
abstract::To explain the lower atmospheric CO2 concentrations during glacial periods, it has been suggested that the productivity of marine phytoplankton was stimulated by an increased flux of iron-bearing dust to the oceans. One component of this theory is that iron-an essential element/nutrient for nitrogen-fixing organisms-w...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/415156a
更新日期:2002-01-10 00:00:00
abstract::The exceptionally broad species diversity of vascular plant genera in east Asian temperate forests, compared with their sister taxa in North America, has been attributed to the greater climatic diversity of east Asia, combined with opportunities for allopatric speciation afforded by repeated fragmentation and coalesce...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35093166
更新日期:2001-09-13 00:00:00
abstract::Transection of a sensory nerve in adults results in profound abnormalities in sensory perception, even if the severed nerve is surgically repaired to facilitate accurate nerve regeneration. In marked contrast, fewer perceptual errors follow nerve transection and surgical repair in children. The basis for this superior...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/381069a0
更新日期:1996-05-02 00:00:00
abstract::Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation. During screening of a murine choroid plexus complementary DNA library, we identified a new chemokine, designated neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern, Cys-X...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/42491
更新日期:1997-06-05 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,新闻
doi:10.1038/d41586-018-07224-0
更新日期:2018-11-01 00:00:00
abstract::Neurotransmitters modulate the activity of ion channels through a variety of second messengers, including cyclic AMP, cyclic GMP and the products of phosphatidylinositol breakdown. Little is known about how different transmitters acting through different second-messenger systems interact within a cell to regulate sing...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/325153a0
更新日期:1987-01-08 00:00:00
abstract::Recognition of self-antigen-derived epitopes presented by major histocompatibility complex class II (MHC II) molecules on thymic epithelial cells (TECs) is critical for the generation of a functional and self-tolerant CD4 T-cell repertoire. Whereas haematopoietic antigen-presenting cells generate MHC-II-peptide comple...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07208
更新日期:2008-09-18 00:00:00
abstract::Synaptic transmission of most vertebrate synapses is thought to be terminated by rapid transport of the neurotransmitter into presynaptic nerve terminals or neuroglia. L-Glutamate is the major excitatory transmitter in brain and its transport represents the mechanism by which it is removed from the synaptic cleft and ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/360464a0
更新日期:1992-12-03 00:00:00
abstract::Complementary DNAs for two distinct anglerfish somatostatin peptides (termed I and II) have been cloned in bacterial plasmids and sequenced. The nucleotide sequence for somatostatin I encodes a large percursor peptide (molecular weight 13,300) in which the somatostatin hormones is at the carboxyl terminus. The predict...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/288137a0
更新日期:1980-11-13 00:00:00
abstract::Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35079135
更新日期:2001-05-31 00:00:00
abstract::The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/26155
更新日期:1998-09-17 00:00:00
abstract::Mammalian neurons contain at least three types of excitatory amino-acid receptors, selectively activated by N-methyl-D-aspartate (NMDA) or aspartate, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate ((S)-AMPA) and kainate. An important aspect of NMDA receptors is their regulation by a variety of factors such...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/345347a0
更新日期:1990-05-24 00:00:00
abstract::Galaxies congregate in clusters and along filaments, and are missing from large regions referred to as voids. These structures are seen in maps derived from spectroscopic surveys that reveal networks of structure that are interconnected with no clear boundaries. Extended regions with a high concentration of galaxies a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13674
更新日期:2014-09-04 00:00:00
abstract::Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine, which stimulated work leading to the development of modern computers. The Turing machine and its special cases, including finite automata, o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35106533
更新日期:2001-11-22 00:00:00
abstract::Broad and deep tumour genome sequencing has shed new light on tumour heterogeneity and provided important insights into the evolution of metastases arising from different clones. There is an additional layer of complexity, in that tumour evolution may be influenced by selective pressure provided by therapy, in a simil...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13948
更新日期:2015-02-12 00:00:00
abstract::The discovery of four new Xenoturbella species from deep waters of the eastern Pacific Ocean is reported here. The genus and two nominal species were described from the west coast of Sweden, but their taxonomic placement remains unstable. Limited evidence placed Xenoturbella with molluscs, but the tissues can be conta...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16545
更新日期:2016-02-04 00:00:00
abstract::Guard cells are located in the epidermis of plant leaves, and in pairs surround stomatal pores. These control both the influx of CO2 as a raw material for photosynthesis and water loss from plants through transpiration to the atmosphere. Guard cells have become a highly developed system for dissecting early signal tra...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/35066500
更新日期:2001-03-15 00:00:00
abstract::Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06489
更新日期:2008-01-17 00:00:00
abstract::External agents of mortality (disturbances) occur over a wide range of scales of space and time, and are believed to have large effects on species diversity. The "intermediate disturbance hypothesis", which proposes maximum diversity at intermediate frequencies of disturbance, has received support from both field and ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35050080
更新日期:2000-12-21 00:00:00
abstract::The neural substrates that the fruitfly Drosophila uses to sense smell, taste and light share marked structural and functional similarities with ours, providing attractive models to dissect sensory stimulus processing. Here we focus on two of the remaining and less understood prime sensory modalities: graviception and...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07810
更新日期:2009-03-12 00:00:00
abstract::Fas is a type-I membrane protein that transduces an apoptotic signal. Binding of Fas ligand or agonistic anti-Fas antibody to Fas kills the cells by apoptosis. Studies in the nematode Caenorhabditis elegans have suggested that proteases such as interleukin-1 beta-converting enzyme (ICE) or the product of the C. elegan...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/375078a0
更新日期:1995-05-04 00:00:00
abstract::The Environmental Protection Agency is preparing to regulate the biotechnology industry, claiming authority under the provisions of the Federal Toxic Substances Control Act (TOSCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). In the agency's view, the products of recombinant DNA techniques can...
journal_title:Nature
pub_type: 新闻
doi:10.1038/306005a0
更新日期:1983-11-03 00:00:00
abstract::Specific genes can be inactivated or mutated in the mouse germ line. The phenotypic consequences of the mutation can provide pivotal information on the function of the gene in development and maintenance of the mammalian organism. The procedure entails homologous recombination in embryonic stem cells, which, on fusion...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/348649a0
更新日期:1990-12-13 00:00:00