Abstract:
:It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.
journal_name
Proc Natl Acad Sci U S Aauthors
Occhetta P,Pigeot S,Rasponi M,Dasen B,Mehrkens A,Ullrich T,Kramer I,Guth-Gundel S,Barbero A,Martin Idoi
10.1073/pnas.1720658115subject
Has Abstractpub_date
2018-05-01 00:00:00pages
4625-4630issue
18eissn
0027-8424issn
1091-6490pii
1720658115journal_volume
115pub_type
杂志文章abstract::The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including gro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.7.3038
更新日期:1993-04-01 00:00:00
abstract::Given the known neuroreparative actions of IL-33 in experimental models of central nervous system (CNS) injury, we predicted that compounds which induce IL-33 are likely to promote remyelination. We found anacardic acid as a candidate molecule to serve as a therapeutic agent to promote remyelination. Addition of anaca...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2006566117
更新日期:2020-09-01 00:00:00
abstract::We have studied the effect of the 3' terminal CCA sequence in precursors of tRNAs on catalysis by the RNase P RNA or the holoenzyme from the cyanobacterium Synechocystis sp. PCC 6803 in a completely homologous system. We have found that the absence of the 3' terminal CCA is not detrimental to activity, which is in sha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.12.6672
更新日期:1999-06-08 00:00:00
abstract::We report here the reconstitution of a pathway that leads to the apoptotic changes in nuclei by using recombinant DNA fragmentation factor (DFF), a heterodimeric protein of 40 and 45 kDa. Coexpression of DFF40 and DFF45 is required to generate recombinant DFF, which becomes activated when DFF45 is cleaved by caspase-3...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.15.8461
更新日期:1998-07-21 00:00:00
abstract::Vertebrae are derived from the sclerotomal moities of the somites. Sclerotomal cells migrate ventrally to surround the notochord, where they form the vertebral body, and dorsolaterally to form the neural arch, which is dorsally closed by the spinous process. Precursor cells of the spinous process as well as superficia...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.22.10435
更新日期:1994-10-25 00:00:00
abstract::Chick calvaria labeled in vitro contain a triple-stranded collagen precursor that contains two pro alpha1 and one pro alpha2 chains. All chains contain cystine and are linked by S-S bonds. Ultracentrifugal analysis was used to measure the relative size of the disulfide-linked units. It is proposed that the S-S links h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.10.2993
更新日期:1973-10-01 00:00:00
abstract::A decade ago, it seemed rational that our rapidly increasing knowledge of the molecular identities of tumor antigens and a deeper understanding of basic immunology would point the way to an effective therapeutic cancer vaccine. Significant progress has been made, but we do not yet have a cancer vaccine that can reliab...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.0404839101
更新日期:2004-10-05 00:00:00
abstract::Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that acco...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1620508114
更新日期:2017-03-21 00:00:00
abstract::We report the heavy chain variable region sequences from the cDNAs of five previously described monoclonal cell lines producing human antibodies specific for the human immunodeficiency virus type 1 and detail the molecular characteristics, germ-line origins, and extent of somatic mutation among these antibodies. Three...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.17.7783
更新日期:1991-09-01 00:00:00
abstract::Adult workers in honeybee (Apis mellifera) colonies exhibit plasticity in hormonally regulated, age-based division of labor by altering their pattern of behavioral development in response to changes in colony conditions. One form of this plasticity is precocious development: levels of juvenile hormone increase prematu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.24.11726
更新日期:1992-12-15 00:00:00
abstract::DNA replication intermediates in human melanoma cells have been investigated by using the drug aphidicolin, which inhibits DNA polymerase alpha. In untreated cells, Okazaki fragments and 10-kilobase (kb) DNA intermediates are formed. In aphidicolin-treated cells, the replication fork is stopped and there is no formati...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.13.3996
更新日期:1983-07-01 00:00:00
abstract::Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy recepto...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1424236112
更新日期:2015-06-09 00:00:00
abstract::RNA interference (RNAi) is triggered in eukaryotic organisms by double-stranded RNA (dsRNA), and it destroys any mRNA that has sequence identity with the dsRNA trigger. The RNAi pathway in Anopheles gambiae can be silenced by transfecting cells with dsRNA derived from exon sequence of the A. gambiae Argonaute2 (AgAgo2...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0406983101
更新日期:2004-12-07 00:00:00
abstract::Embryonal kidney cell tumors develop in rats given the alkylating agent N-nitroso-N'-methylurea as neonates. These tumors resemble the childhood Wilms tumors in their histopathology. Deletions and mutations in the Wilms tumor suppressor gene, WT1, are present in up to 6% of childhood nephroblastomas. To investigate th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.21.9931
更新日期:1994-10-11 00:00:00
abstract::Phospholipase C-gamma1 (PLC-gamma1) contains two tandem Src homology 2 (SH2) domains. The NH(2)-terminal SH2 domain has been known to mediate the binding of PLC-gamma1 to receptor protein tyrosine kinases, which then activate PLC-gamma1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY7...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0409590102
更新日期:2005-03-22 00:00:00
abstract::Trafficking and turnover of transmitter receptors required to maintain and modify the strength of chemical synapses have been characterized extensively. In contrast, little is known regarding trafficking of gap junction components at electrical synapses. By combining ultrastructural and in vivo physiological analysis ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1121557109
更新日期:2012-02-28 00:00:00
abstract::The growth of colloidal metal nanocrystals typically involves an autocatalytic process, in which the salt precursor adsorbs onto the surface of a growing nanocrystal, followed by chemical reduction to atoms for their incorporation into the nanocrystal. Despite its universal role in the synthesis of colloidal nanocryst...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1713907114
更新日期:2017-12-26 00:00:00
abstract::Given the slow unfolding of what may become catastrophic changes to Earth's climate, many are understandably distraught by failures of public policy to rise to the magnitude of the challenge. Few in the science community would think to question the scientific response to the unfolding changes. However, is the science ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1906691116
更新日期:2019-12-03 00:00:00
abstract::Cyanogen bromide fragments were isolated from the heavy chains of three human IgG myeloma proteins of the V(H)III subgroup, sequenced by an automated method, and localized to the variable region. Inspection of these sequences, together with corresponding stretches from both human and animal proteins (studied in other ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.9.2019
更新日期:1971-09-01 00:00:00
abstract::Smooth muscle cells use fibronectin to bind to type I and type III collagens but bind to type V collagen by a trypsin-resistant intrinsic glycoconjugate. The binding site on type V collagen is located in the alpha A chain. By using collagen-coated filters in a modified Boyden chamber assay for chemotaxis, it was obser...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.6.3669
更新日期:1981-06-01 00:00:00
abstract::Brown adipose tissue (BAT) is present throughout life in rodents and plays an important role in energy balance. However, whereas BAT is clearly recognizable in the neonates of larger mammals (including dogs, cats, sheep, cattle, and humans), it is undetectable or present in only small quantities in adults of these spe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.23.10774
更新日期:1991-12-01 00:00:00
abstract::The 369-residue glycoprotein D (gD) is the entry, receptor-binding protein of herpes simplex virus 1. The common receptors for viral entry are nectin-1, HveA, and a specific O-linked sulfated proteoglycan. The major receptor-binding sites of gD are at the N terminus, whereas the domain required for fusion of viral env...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611565104
更新日期:2007-03-06 00:00:00
abstract::The amount of extra-pair paternity in socially monogamous bird species varies from 0% to 76% extra-pair offspring. The causes of this remarkable interspecific variation are largely unknown, although intraspecific analyses suggest that females seek extra-pair matings to improve the genetic quality of their offspring. I...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.16.9390
更新日期:1998-08-04 00:00:00
abstract::The dilute (d) coat color mutation on chromosome 9 is closely associated with an ecotropic murine leukemia virus (MuLV) genome [Jenkins, N.A., Copeland, N.G., Taylor, B.A. & Lee, B.K. (1981) Nature 293, 370-374]. DBA/2J mice homozygous for the reverse mutation to wild type at the dilute locus (d+2J) lack ecotropic vir...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.1.247
更新日期:1983-01-01 00:00:00
abstract::Nascent precursors of phosphatidylinositol-glycan (PI-G)-linked membrane proteins contain a hydrophobic COOH-terminal sequence of 15-30 residues that is eliminated during processing to yield a newly exposed COOH terminus to which the PI-G moiety is added. There is no consensus as to the primary structure of the termin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.20.7939
更新日期:1990-10-01 00:00:00
abstract::Spinach chloroplasts were found to contain three forms of cytochrome b(559) that have the same alpha-peak at 559 nm, but are distinguished from one another by their oxidation-reduction potentials. The high-potential (H) form (E(m) about 330-350 mV) is reducible by hydroquinone, the middle-potential (M) form (E(m) abou...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.12.3064
更新日期:1971-12-01 00:00:00
abstract::In order to retain in an in situ system the control mechanisms involved in synthesis of bacteriophage T4 DNA, infected cells were made permeable to nucleotides by plasmolysis with concentrated sucrose. Such preparations use exogenous deoxyribonucleotides to synthesize T4 phage DNA. As has been observed with in vivo st...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.8.2196
更新日期:1973-08-01 00:00:00
abstract::Coxsackievirus causes severe disease in adult mice subjected to sustained post-weaning undernutrition (marasmus). Virus-infected marasmic mice have an increased incidence of mortality, severe lesions, and elevated and persistent viral in target organs. Transfer of immune lymphoid cells 30 min or 24 hr after viral chal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.9.2108
更新日期:1971-09-01 00:00:00
abstract::Converging evidence from electrophysiological recording and lesion studies suggests an essential role for the cerebellum in classical conditioning of the nictitating membrane response in the rabbit. The present study begins to delineate within this structure neurotransmitter systems that appear critical for the expres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.7.2101
更新日期:1987-04-01 00:00:00
abstract::We compared folding properties of designed protein Top7 and natural protein S6 by using coarse-grained chain models with a mainly native-centric construct that accounted also for nonnative hydrophobic interactions and desolvation barriers. Top7 and S6 have similar secondary structure elements and are approximately equ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0911844107
更新日期:2010-02-16 00:00:00