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Lymphatic vessels in bone support regeneration after injury.

Cell | 2023

Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate osteogenesis and hematopoiesis, but current dogma suggests that bone lacks lymphatic vessels. Here, by combining high-resolution light-sheet imaging and cell-specific mouse genetics, we demonstrate presence of lymphatic vessels in mouse and human bones. We find that lymphatic vessels in bone expand during genotoxic stress. VEGF-C/VEGFR-3 signaling and genotoxic stress-induced IL6 drive lymphangiogenesis in bones. During lymphangiogenesis, secretion of CXCL12 from proliferating lymphatic endothelial cells is critical for hematopoietic and bone regeneration. Moreover, lymphangiocrine CXCL12 triggers expansion of mature Myh11+ CXCR4+ pericytes, which differentiate into bone cells and contribute to bone and hematopoietic regeneration. In aged animals, such expansion of lymphatic vessels and Myh11-positive cells in response to genotoxic stress is impaired. These data suggest lymphangiogenesis as a therapeutic avenue to stimulate hematopoietic and bone regeneration.

Pubmed ID: 36669473 RIS Download

Additional research tools detected in this publication

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Antibodies used in this publication

Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 202300/Z/16/Z
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UP_1605/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/P02209X/1

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Ki67 antibody - Proliferation Marker (antibody)

RRID:AB_443209

This polyclonal targets Ki67 antibody - Proliferation Marker

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Rabbit Anti-LYVE1 Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_301509

This polyclonal targets LYVE1 - Lymphatic Vessel Marker

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Anti-SOX9 antibody (antibody)

RRID:AB_2728660

This monoclonal targets SOX9

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APC anti-mouse CD3 (antibody)

RRID:AB_2561456

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APC anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)

RRID:AB_313376

This monoclonal targets Ly-6G Ly-6C

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Fibronectin antibody (antibody)

RRID:AB_2262874

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Anti-FSP1/S100A4 (antibody)

RRID:AB_10807552

This polyclonal targets FSP1/S100A4

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Mouse VE-Cadherin Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2077789

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PE anti-mouse CD45 (antibody)

RRID:AB_312970

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CD68 antibody [FA-11] (Biotin) (antibody)

RRID:AB_11166091

This monoclonal targets CD68 antibody [FA-11] ()

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Mouse/Rat CD31/PECAM-1 Antibody (antibody)

RRID:AB_2161028

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CD45R (B220)-Biotin, mouse (antibody)

RRID:AB_2660454

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PE Anti-Mouse CD8a (53-6.7) (antibody)

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APC anti-mouse CD2 (antibody)

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FITC anti-mouse Ly-6A/E (Sca-1) (antibody)

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CD48 (antibody)

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PE anti-mouse CD150 (SLAM) (antibody)

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CXCR4 antibody [UMB2] (antibody)

RRID:AB_10975635

This monoclonal targets CXCR4 antibody [UMB2]

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ICAM1 antibody [EP1442Y] (antibody)

RRID:AB_870702

This monoclonal targets Human ICAM1

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Anti-NG2 Chondroitin Sulfate Proteoglycan (antibody)

RRID:AB_91789

This polyclonal targets NG2 Chondroitin Sulfate Proteoglycan

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Mouse E-Cadherin Affinity Purified Polyclonal Ab (antibody)

RRID:AB_355568

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Osteocalcin Polyclonal Antibody (antibody)

RRID:AB_2745986

This unknown targets Osteocalcin

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Osteocalcin antibody (antibody)

RRID:AB_10675660

This polyclonal targets Osteocalcin antibody

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Mouse Decorin Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2090386

This polyclonal targets Mouse Decorin Affinity Purified Ab

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Mouse Podocalyxin Affinity Purified Polyclonal Ab (antibody)

RRID:AB_354858

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Anti-OSX Antibody (F-3) (antibody)

RRID:AB_2895257

This monoclonal targets OSX

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Anti- Heparan Sulfate Proteoglycan (Perlecan), clone A7L6 (antibody)

RRID:AB_10615958

This monoclonal targets Heparan Sulfate Proteoglycan (Perlecan) clone A7L6

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Recombinant Anti-PDGFR beta antibody [Y92] - C-terminal (antibody)

RRID:AB_777165

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PROX1 antibody (antibody)

RRID:AB_10712211

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Mouse Podoplanin Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2268062

This polyclonal targets Mouse Podoplanin Affinity Purified Ab

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IL-6 Receptor Polyclonal Antibody (antibody)

RRID:AB_2609193

This unknown targets IL-6 Receptor

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Perilipin (D1D8) XP Rabbit mAb (antibody)

RRID:AB_10829911

This monoclonal targets Perilipin

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Mouse Osteopontin (OPN) Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2194992

This polyclonal targets Mouse Osteopontin (OPN) Affinity Purified Ab

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Human Endoglin/CD105 Affinity Purified Polyclonal Ab (antibody)

RRID:AB_354598

This polyclonal targets Human Endoglin/CD105 Affinity Purified Ab

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Mouse Endoglin/CD105 Affinity Purified Polyclonal Ab (antibody)

RRID:AB_354735

This polyclonal targets Mouse Endoglin/CD105 Affinity Purified Ab

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Anti-TAGLN/Transgelin antibody (antibody)

RRID:AB_443021

This polyclonal targets TAGLN/Transgelin

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Endomucin (V.7C7) (antibody)

RRID:AB_2100037

This monoclonal targets Mouse Endomucin

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Monoclonal Anti-Actin, alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse (antibody)

RRID:AB_476856

This monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse

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B6;129P2-Lyve1tm1.1(EGFP/cre)Cys/J (organism)

RRID:IMSR_JAX:012601

Mus musculus with name B6;129P2-Lyve1tm1.1(EGFP/cre)Cys/J from IMSR.

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C57BL/6-Tg(Adipoq-icre/ERT2)1Soff/J (organism)

RRID:IMSR_JAX:025124

Mus musculus with name C57BL/6-Tg(Adipoq-icre/ERT2)1Soff/J from IMSR.

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B6.Cg-Tg(Cspg4-cre/Esr1*)BAkik/J (organism)

RRID:IMSR_JAX:008538

Mus musculus with name B6.Cg-Tg(Cspg4-cre/Esr1*)BAkik/J from IMSR.

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STOCK Gli1tm3(cre/ERT2)Alj/J (organism)

RRID:IMSR_JAX:007913

Mus musculus with name STOCK Gli1tm3(cre/ERT2)Alj/J from IMSR.

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129S/SvJae-Pdgfrbtm11Sor/J (organism)

RRID:IMSR_JAX:010977

Mus musculus with name 129S/SvJae-Pdgfrbtm11Sor/J from IMSR.

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STOCK Gt(ROSA)26Sortm1(DTA)Jpmb/J (organism)

RRID:IMSR_JAX:006331

Mus musculus with name STOCK Gt(ROSA)26Sortm1(DTA)Jpmb/J from IMSR.

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STOCK Cxcl12tm1.1Sjm/J (organism)

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Mus musculus with name STOCK Cxcl12tm1.1Sjm/J from IMSR.

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STOCK Prox1tm3(cre/ERT2)Gco/J (organism)

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Mus musculus with name STOCK Prox1tm3(cre/ERT2)Gco/J from IMSR.

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B6.129S2-Il6tm1Kopf/J (organism)

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Mus musculus with name B6.129S2-Il6tm1Kopf/J from IMSR.

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B6.FVB-Tg(Myh11-icre/ERT2)1Soff/J (organism)

RRID:IMSR_JAX:019079

Mus musculus with name B6.FVB-Tg(Myh11-icre/ERT2)1Soff/J from IMSR.

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