Osteoblast-derived paracrine factors regulate angiogenesis in response to mechanical stimulation

Chao Liu, Xin Cui, Thomas M. Ackermann, Vittoria Flamini, Weiqiang Chen, Alesha Castillo

Research output: Contribution to journalArticle

Abstract

Angiogenesis is a process by which new blood vessels emerge from existing vessels through endothelial cell sprouting, migration, proliferation, and tubule formation. Angiogenesis during skeletal growth, homeostasis and repair is a complex and incompletely understood process. As the skeleton adapts to mechanical loading, we hypothesized that mechanical stimulation regulates "osteo-angio" crosstalk in the context of angiogenesis. We showed that conditioned media (CM) from osteoblasts exposed to fluid shear stress enhanced endothelial cell proliferation and migration, but not tubule formation, relative to CM from static cultures. Endothelial cell sprouting was studied using a dual-channel collagen gel-based microfluidic device that mimics vessel geometry. Static CM enhanced endothelial cell sprouting frequency, whereas loaded CM significantly enhanced both frequency and length. Both sprouting frequency and length were significantly enhanced in response to factors released from osteoblasts exposed to fluid shear stress in an adjacent channel. Osteoblasts released angiogenic factors, of which osteopontin, PDGF-AA, IGBP-2, MCP-1, and Pentraxin-3 were upregulated in response to mechanical loading. These data suggest that in vivo mechanical forces regulate angiogenesis in bone by modulating "osteo-angio" crosstalk through release of paracrine factors, which we term "osteokines".

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalIntegrative Biology (United Kingdom)
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Angiogenesis Inducing Agents
Osteoblasts
Endothelial cells
Conditioned Culture Medium
Endothelial Cells
Lab-On-A-Chip Devices
Crosstalk
Cell Movement
Shear stress
Osteopontin
Fluids
Blood vessels
Cell proliferation
Cell culture
Microfluidics
Skeleton
Blood Vessels
Bone
Homeostasis
Repair

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Osteoblast-derived paracrine factors regulate angiogenesis in response to mechanical stimulation. / Liu, Chao; Cui, Xin; Ackermann, Thomas M.; Flamini, Vittoria; Chen, Weiqiang; Castillo, Alesha.

In: Integrative Biology (United Kingdom), Vol. 8, No. 7, 01.07.2016, p. 785-794.

Research output: Contribution to journalArticle

@article{c9e75cf8439f4886a361598f52117e7b,
title = "Osteoblast-derived paracrine factors regulate angiogenesis in response to mechanical stimulation",
abstract = "Angiogenesis is a process by which new blood vessels emerge from existing vessels through endothelial cell sprouting, migration, proliferation, and tubule formation. Angiogenesis during skeletal growth, homeostasis and repair is a complex and incompletely understood process. As the skeleton adapts to mechanical loading, we hypothesized that mechanical stimulation regulates {"}osteo-angio{"} crosstalk in the context of angiogenesis. We showed that conditioned media (CM) from osteoblasts exposed to fluid shear stress enhanced endothelial cell proliferation and migration, but not tubule formation, relative to CM from static cultures. Endothelial cell sprouting was studied using a dual-channel collagen gel-based microfluidic device that mimics vessel geometry. Static CM enhanced endothelial cell sprouting frequency, whereas loaded CM significantly enhanced both frequency and length. Both sprouting frequency and length were significantly enhanced in response to factors released from osteoblasts exposed to fluid shear stress in an adjacent channel. Osteoblasts released angiogenic factors, of which osteopontin, PDGF-AA, IGBP-2, MCP-1, and Pentraxin-3 were upregulated in response to mechanical loading. These data suggest that in vivo mechanical forces regulate angiogenesis in bone by modulating {"}osteo-angio{"} crosstalk through release of paracrine factors, which we term {"}osteokines{"}.",
author = "Chao Liu and Xin Cui and Ackermann, {Thomas M.} and Vittoria Flamini and Weiqiang Chen and Alesha Castillo",
year = "2016",
month = "7",
day = "1",
doi = "10.1039/c6ib00070c",
language = "English (US)",
volume = "8",
pages = "785--794",
journal = "Integrative Biology",
issn = "1757-9694",
publisher = "Royal Society of Chemistry",
number = "7",

}

TY - JOUR

T1 - Osteoblast-derived paracrine factors regulate angiogenesis in response to mechanical stimulation

AU - Liu, Chao

AU - Cui, Xin

AU - Ackermann, Thomas M.

AU - Flamini, Vittoria

AU - Chen, Weiqiang

AU - Castillo, Alesha

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Angiogenesis is a process by which new blood vessels emerge from existing vessels through endothelial cell sprouting, migration, proliferation, and tubule formation. Angiogenesis during skeletal growth, homeostasis and repair is a complex and incompletely understood process. As the skeleton adapts to mechanical loading, we hypothesized that mechanical stimulation regulates "osteo-angio" crosstalk in the context of angiogenesis. We showed that conditioned media (CM) from osteoblasts exposed to fluid shear stress enhanced endothelial cell proliferation and migration, but not tubule formation, relative to CM from static cultures. Endothelial cell sprouting was studied using a dual-channel collagen gel-based microfluidic device that mimics vessel geometry. Static CM enhanced endothelial cell sprouting frequency, whereas loaded CM significantly enhanced both frequency and length. Both sprouting frequency and length were significantly enhanced in response to factors released from osteoblasts exposed to fluid shear stress in an adjacent channel. Osteoblasts released angiogenic factors, of which osteopontin, PDGF-AA, IGBP-2, MCP-1, and Pentraxin-3 were upregulated in response to mechanical loading. These data suggest that in vivo mechanical forces regulate angiogenesis in bone by modulating "osteo-angio" crosstalk through release of paracrine factors, which we term "osteokines".

AB - Angiogenesis is a process by which new blood vessels emerge from existing vessels through endothelial cell sprouting, migration, proliferation, and tubule formation. Angiogenesis during skeletal growth, homeostasis and repair is a complex and incompletely understood process. As the skeleton adapts to mechanical loading, we hypothesized that mechanical stimulation regulates "osteo-angio" crosstalk in the context of angiogenesis. We showed that conditioned media (CM) from osteoblasts exposed to fluid shear stress enhanced endothelial cell proliferation and migration, but not tubule formation, relative to CM from static cultures. Endothelial cell sprouting was studied using a dual-channel collagen gel-based microfluidic device that mimics vessel geometry. Static CM enhanced endothelial cell sprouting frequency, whereas loaded CM significantly enhanced both frequency and length. Both sprouting frequency and length were significantly enhanced in response to factors released from osteoblasts exposed to fluid shear stress in an adjacent channel. Osteoblasts released angiogenic factors, of which osteopontin, PDGF-AA, IGBP-2, MCP-1, and Pentraxin-3 were upregulated in response to mechanical loading. These data suggest that in vivo mechanical forces regulate angiogenesis in bone by modulating "osteo-angio" crosstalk through release of paracrine factors, which we term "osteokines".

UR - http://www.scopus.com/inward/record.url?scp=84978389609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978389609&partnerID=8YFLogxK

U2 - 10.1039/c6ib00070c

DO - 10.1039/c6ib00070c

M3 - Article

C2 - 27332785

AN - SCOPUS:84978389609

VL - 8

SP - 785

EP - 794

JO - Integrative Biology

JF - Integrative Biology

SN - 1757-9694

IS - 7

ER -