CD73/5'-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells
Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and...
Saved in:
Published in | European cells & materials Vol. 25; pp. 37 - 47 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Forum Multimedia Publishing LLC
08.01.2013
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and matrix assembly, but also reduces the expression of CD73, an ecto-5'-nucleotidase, which plays a crucial role in extracellular adenosine generation. Although, for almost 20 years, CD73 has been a major cell surface marker defining MSCs, little is known about its function in these cells. Therefore, the aim of this study was to determine the putative involvement of CD73 in MSC differentiation after cyclic-compressive loading. After cultivation in appropriate differentiation media, chondrogenic differentiation ability was significantly increased in loaded MSCs, hence following current models. Through treatment with the CD73 inhibitor adenosine 5'-(α, β-methylene) diphosphate, chondrogenic matrix deposition was further increased; in contrast, mineral matrix deposition and expression of osteogenic markers was reduced. One major signal transduction pathway, which is activated via CD73-mediated adenosine, is the adenosine receptor pathway. Thus, the adenosine receptor expression pattern was investigated. MSCs expressed the four known adenosine receptors at the mRNA level. After mechanical stimulation of MSCs, Adora2a was down-regulated. These data point towards a role of CD73 in MSC differentiation possibly via A2AR signalling, which is mutually regulated with CD73. In conclusion, the findings of this study suggest that CD73 is another regulatory factor in osteo-/chondrogenic differentiation of MSCs and may provide a - thus far underestimated - therapeutic target to guide bone regeneration. |
---|---|
AbstractList | Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and matrix assembly, but also reduces the expression of CD73, an ecto-5'-nucleotidase, which plays a crucial role in extracellular adenosine generation. Although, for almost 20 years, CD73 has been a major cell surface marker defining MSCs, little is known about its function in these cells. Therefore, the aim of this study was to determine the putative involvement of CD73 in MSC differentiation after cyclic-compressive loading. After cultivation in appropriate differentiation media, chondrogenic differentiation ability was significantly increased in loaded MSCs, hence following current models. Through treatment with the CD73 inhibitor adenosine 5'-(α, β-methylene) diphosphate, chondrogenic matrix deposition was further increased; in contrast, mineral matrix deposition and expression of osteogenic markers was reduced. One major signal transduction pathway, which is activated via CD73-mediated adenosine, is the adenosine receptor pathway. Thus, the adenosine receptor expression pattern was investigated. MSCs expressed the four known adenosine receptors at the mRNA level. After mechanical stimulation of MSCs, Adora2a was down-regulated. These data point towards a role of CD73 in MSC differentiation possibly via A2AR signalling, which is mutually regulated with CD73. In conclusion, the findings of this study suggest that CD73 is another regulatory factor in osteo-/chondrogenic differentiation of MSCs and may provide a - thus far underestimated - therapeutic target to guide bone regeneration. |
Author | Ode, A Duda, G N Schoon, J Gaetjen, M Ode, J E Geissler, S Kurtz, A |
Author_xml | – sequence: 1 givenname: A surname: Ode fullname: Ode, A email: Andrea.Ode@charite.de organization: Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany. Andrea.Ode@charite.de – sequence: 2 givenname: J surname: Schoon fullname: Schoon, J – sequence: 3 givenname: A surname: Kurtz fullname: Kurtz, A – sequence: 4 givenname: M surname: Gaetjen fullname: Gaetjen, M – sequence: 5 givenname: J E surname: Ode fullname: Ode, J E – sequence: 6 givenname: S surname: Geissler fullname: Geissler, S – sequence: 7 givenname: G N surname: Duda fullname: Duda, G N |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23300031$$D View this record in MEDLINE/PubMed |
BookMark | eNpNkU1v1DAQhi1URD_gxhn5Bpd0HY8TZ49o-WilSlzgHE3s8a6rxC62g7Q_o_8YLy0IaaR39Pr1M7Lnkp2FGIixt624llIK2JBZrn8J2aGAF-yiVRoaKXt59l9_zi5zvhdCQr3xip1LACEEtBfscfdJw6Z735ApsQmrmSkWbzETR1Myx1o80X6dscR05K66MXEfeMyFYrMxhxhsinsK3nDrnaNEoXgsPtaM4wuZA9YznOcjz8UvJxLZ6mcK5nBccK52iic1NM_5NXvpcM705lmv2I8vn7_vbpq7b19vdx_vGqNAlUZNvZESlOkJh4GIlJu63vYgpq0QSm019tsJtzRgJ6RrLWndT12rQdhpQIArdvvEtRHvx4fkF0zHMaIf_xgx7UdMxdcPGcmQBZC6s2BV6-zgBotW645kxZm-sj48sR5S_LlSLuPi8-k1GCiueWxrDrq6Dlmj756j67SQ_Tf470rgN6zOkcI |
CitedBy_id | crossref_primary_10_1002_med_21796 crossref_primary_10_1016_j_cellsig_2016_09_008 crossref_primary_10_3390_ijms18112391 crossref_primary_10_1016_j_biomaterials_2016_04_023 crossref_primary_10_1016_j_imbio_2016_01_013 crossref_primary_10_1002_jcp_27694 crossref_primary_10_1089_scd_2014_0349 crossref_primary_10_1002_advs_202000412 crossref_primary_10_1021_acs_biomac_1c00205 crossref_primary_10_3389_fbioe_2022_953034 crossref_primary_10_3390_vetsci10120673 crossref_primary_10_5966_sctm_2015_0148 crossref_primary_10_1016_j_msec_2020_111518 crossref_primary_10_7124_visnyk_utgis_14_1_541 crossref_primary_10_4252_wjsc_v6_i2_153 crossref_primary_10_1002_jcb_25239 crossref_primary_10_1016_j_bonr_2021_101133 crossref_primary_10_1016_j_jcms_2015_04_012 crossref_primary_10_1002_jcp_25303 crossref_primary_10_1016_j_csbj_2014_11_003 crossref_primary_10_12923_j_2084_980X_26_4_a_02 crossref_primary_10_1016_j_stemcr_2017_08_007 crossref_primary_10_1038_s41598_017_06780_1 crossref_primary_10_1186_s13287_023_03552_9 crossref_primary_10_1007_s10753_018_0781_z crossref_primary_10_1177_08853282231153725 crossref_primary_10_1016_j_placenta_2014_11_002 crossref_primary_10_3109_1354750X_2015_1130191 crossref_primary_10_1007_s00106_019_00805_z crossref_primary_10_1007_s11302_019_09656_3 crossref_primary_10_1016_j_bcp_2019_113784 crossref_primary_10_1007_s13770_016_0020_3 crossref_primary_10_1186_s13075_022_02736_7 crossref_primary_10_1016_j_joca_2014_10_001 crossref_primary_10_1089_ten_tea_2018_0311 crossref_primary_10_1097_SCS_0000000000001717 crossref_primary_10_1002_adfm_201401263 crossref_primary_10_1038_s41598_019_41741_w crossref_primary_10_3390_ani14131848 crossref_primary_10_1038_s41598_018_27760_z crossref_primary_10_1186_s13287_020_01714_7 crossref_primary_10_3389_fimmu_2019_02474 crossref_primary_10_1038_s41598_020_62568_w crossref_primary_10_3390_ijms23042038 crossref_primary_10_1016_j_acthis_2016_04_004 crossref_primary_10_1002_jcb_25610 crossref_primary_10_1007_s11914_018_0451_y crossref_primary_10_1186_s13287_015_0263_2 crossref_primary_10_1002_sctm_18_0216 crossref_primary_10_1134_S1990747820030101 crossref_primary_10_1002_jcp_30399 crossref_primary_10_3390_ijms17101654 crossref_primary_10_1016_j_actbio_2016_01_037 crossref_primary_10_3390_ma13235342 crossref_primary_10_1016_j_scr_2015_09_005 crossref_primary_10_1002_jcp_26904 crossref_primary_10_1002_jcb_25664 crossref_primary_10_1002_sctm_17_0137 crossref_primary_10_3389_fcell_2021_637239 crossref_primary_10_1016_j_bcp_2023_115646 crossref_primary_10_1016_j_jcyt_2016_06_005 crossref_primary_10_1002_stem_1831 crossref_primary_10_3389_fbioe_2017_00054 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM 7X8 DOA |
DOI | 10.22203/ecm.v025a03 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic DOAJ Directory of Open Access Journals |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
EISSN | 1473-2262 |
EndPage | 47 |
ExternalDocumentID | oai_doaj_org_article_eced33275d3d41fd8f8dad775e2730c6 23300031 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GroupedDBID | --- 29G 2WC 53G 5GY 5VS ADBBV AENEX ALMA_UNASSIGNED_HOLDINGS BAWUL BCNDV CGR CUY CVF DIK E3Z EBS ECM EIF EJD F5P FRP GROUPED_DOAJ GX1 IPNFZ KQ8 M~E NPM OK1 P2P RIG RNS TR2 XSB 7X8 |
ID | FETCH-LOGICAL-c434t-4b6c2234c6ea88eee4fb56d630b9004497a69ba9e8a502f1de776b51730db8a33 |
IEDL.DBID | DOA |
ISSN | 1473-2262 |
IngestDate | Mon Jul 15 19:33:15 EDT 2024 Thu Apr 11 15:27:45 EDT 2024 Thu May 23 23:55:19 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Language | English |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c434t-4b6c2234c6ea88eee4fb56d630b9004497a69ba9e8a502f1de776b51730db8a33 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
OpenAccessLink | https://doaj.org/article/eced33275d3d41fd8f8dad775e2730c6 |
PMID | 23300031 |
PQID | 1273351472 |
PQPubID | 23479 |
PageCount | 11 |
ParticipantIDs | doaj_primary_oai_doaj_org_article_eced33275d3d41fd8f8dad775e2730c6 proquest_miscellaneous_1273351472 pubmed_primary_23300031 |
PublicationCentury | 2000 |
PublicationDate | 2013-Jan-08 |
PublicationDateYYYYMMDD | 2013-01-08 |
PublicationDate_xml | – month: 01 year: 2013 text: 2013-Jan-08 day: 08 |
PublicationDecade | 2010 |
PublicationPlace | Switzerland |
PublicationPlace_xml | – name: Switzerland |
PublicationTitle | European cells & materials |
PublicationTitleAlternate | Eur Cell Mater |
PublicationYear | 2013 |
Publisher | Forum Multimedia Publishing LLC |
Publisher_xml | – name: Forum Multimedia Publishing LLC |
SSID | ssj0023220 |
Score | 2.3133116 |
Snippet | Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the... |
SourceID | doaj proquest pubmed |
SourceType | Open Website Aggregation Database Index Database |
StartPage | 37 |
SubjectTerms | 5'-Nucleotidase - antagonists & inhibitors 5'-Nucleotidase - metabolism Adenosine Diphosphate - analogs & derivatives Adenosine Diphosphate - pharmacology Alkaline Phosphatase - metabolism Animals Antigens, CD - metabolism CD73/5’-ecto-nucleotidase Cell Differentiation Cell Proliferation Cells, Cultured Chondrogenesis chondrogenic differentiation Gene Expression Male mechanical stimulation Mesenchymal Stem Cells - enzymology Mesenchymal Stem Cells - physiology Mesenchymal stromal cells Osteoblasts - enzymology Osteogenesis osteogenic differentiation Rats Rats, Inbred Lew Receptor, Adenosine A2A - genetics Receptor, Adenosine A2A - metabolism Signal Transduction |
Title | CD73/5'-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells |
URI | https://www.ncbi.nlm.nih.gov/pubmed/23300031 https://search.proquest.com/docview/1273351472 https://doaj.org/article/eced33275d3d41fd8f8dad775e2730c6 |
Volume | 25 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3NbtQwELaqnrhUoEK7UJArcTW7jv-SIy2UCglOVNpb5J-xWIlN0CattLe-AydejyfpTLyLuCAuSFEiWZEz8TfOzDie-Rh7LX3w2UoQFpqGAhQtfE4Y80COIFWofKLk5E-f7fWN_rg0yz-ovmhPWCkPXAZuDhGSUpUzSSUtc6pznXxyzgAa3kUsxbal2QdTu1AL1XRKhdROCXQwqrLlHW3hQmGP6zd3aOo9EWVNhfr_7l1OVubqMTvauYf8bRHrCTuA7pj9uHzn1Nz8uv8paI1ddFSDuB9XCS0Q93EcuMeDbwqtfL_Z8sKiw1cdpxyOXszxI0eVCVBbVpHvSVHGAgvvM18DZQATYN-2HGf9mnqChO0DqvHX7RqFGsZNT1da6x-espur918ur8WOTEFErfQodLARXQEdLfi6BgCdg7HJqkVo6K9u47xtgm-g9mZRZZnAORuMxEFOofZKPWOHXd_BKeNK12BVqnHuR51RBRrjQ0oa-01ZmzhjFzSq7fdSL6OlCtZTA-La7nBt_4XrjJ3vMWlR4-nVfAf97dBKvIHyD1w1YycFrN-PqpSiKE8-_x8ivGCPqon8ghaRz9jhuLmFl-iCjOHVpG14_rCUD1_j4AU |
link.rule.ids | 315,786,790,870,2115,27957,27958 |
linkProvider | Directory of Open Access Journals |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=CD73%2F5%27-ecto-nucleotidase+acts+as+a+regulatory+factor+in+osteo-%2Fchondrogenic+differentiation+of+mechanically+stimulated+mesenchymal+stromal+cells&rft.jtitle=European+cells+%26+materials&rft.au=Ode%2C+A&rft.au=Schoon%2C+J&rft.au=Kurtz%2C+A&rft.au=Gaetjen%2C+M&rft.date=2013-01-08&rft.eissn=1473-2262&rft.volume=25&rft.spage=37&rft.epage=47&rft_id=info:doi/10.22203%2Fecm.v025a03&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1473-2262&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1473-2262&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1473-2262&client=summon |