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Human microvascular endothelial cell activation by IL-1 and TNF-alpha stimulates the adhesion and transendothelial migration of circulating human CD14+ monocytes that develop with RANKL into functional osteoclasts.
J Bone Miner Res. 2006 Feb; 21(2):193-206.JB

Abstract

Circulating pre-OCs may be recruited to locally inflamed sites through specific interactions with activated microvasculature. We found that HMVECs stimulated the adhesion and TEM of circulating pre-OCs, in an ICAM-1- and CD44-dependent manner, leading to greater RANKL-induced OC formation and bone pit resorption.

INTRODUCTION

Inflammation is critical for healing processes but causes severe tissue destruction when chronic. Local osteoclast (OC) formation and bone resorption may increase at inflammatory sites through multiple mechanisms, including direct stimulation by inflamed microvasculature of circulating OC precursor (pre-OC) migration through a blood vessel barrier into bone or joint tissue. How this might occur is not yet well understood.

MATERIALS AND METHODS

Cytokine-activated human microvascular endothelial cell (HMVEC) monolayers, with or without IL-1 and TNF-alpha preactivation (24 h), were incubated in adhesion (1-3 h) or porous transwell transendothelial migration (TEM; 3 h) assays with human peripheral blood mononuclear cells (hPBMCs) or CD14+ monocyte or CD14- lymphocyte subsets. The number of cells that adhered or transmigrated, and their ability to thereafter develop with macrophage-colony stimulating factor (M-CSF) + RANKL into bone pit-resorbing OCs, were analyzed. Immunostaining and neutralizing antibodies to key cell adhesion molecules were used to determine their potential involvement in stimulated CD14+ monocyte TEM.

RESULTS

M-CSF + RANKL caused OC and bone pit formation only from hPBMCs and CD14+ cells but not CD14- cells. Adhesion of hPBMCs or CD14+ cells but not CD14- cells was stimulated by cytokine preactivation of HMVECs and led to the full capture of all circulating pre-OCs capable of developing into OCs. Cytokine-preactivated HMVECs also promoted the postadhesion TEM of hPBMCs and CD14+ populations, resulting in markedly greater OC formation and bone pit resorption by transmigrated cells. Immunodetectable vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and CD44 levels increased on cytokine-treated HMVEC surfaces, and neutralizing antibodies to ICAM-1 or CD44, but not VCAM-1 or platelet endothelial cell adhesion molecule (PECAM-1), inhibited stimulated CD14+ cell TEM through activated HMVECs.

CONCLUSIONS

This is the first demonstration that cytokine-activated HMVECs efficiently capture and promote the TEM of circulating pre-OCs capable of differentiating into bone-resorbing OCs. Thus, direct pre-OC recruitment by activated microvasculature at inflammatory sites may significantly contribute to normal OC bone remodeling during fracture healing or exacerbate pathological bone loss in various chronic inflammatory disorders.

Authors+Show Affiliations

Department of Biology, Washington University, St Louis, Missouri, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16418775

Citation

Kindle, Libby, et al. "Human Microvascular Endothelial Cell Activation By IL-1 and TNF-alpha Stimulates the Adhesion and Transendothelial Migration of Circulating Human CD14+ Monocytes That Develop With RANKL Into Functional Osteoclasts." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 21, no. 2, 2006, pp. 193-206.
Kindle L, Rothe L, Kriss M, et al. Human microvascular endothelial cell activation by IL-1 and TNF-alpha stimulates the adhesion and transendothelial migration of circulating human CD14+ monocytes that develop with RANKL into functional osteoclasts. J Bone Miner Res. 2006;21(2):193-206.
Kindle, L., Rothe, L., Kriss, M., Osdoby, P., & Collin-Osdoby, P. (2006). Human microvascular endothelial cell activation by IL-1 and TNF-alpha stimulates the adhesion and transendothelial migration of circulating human CD14+ monocytes that develop with RANKL into functional osteoclasts. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 21(2), 193-206.
Kindle L, et al. Human Microvascular Endothelial Cell Activation By IL-1 and TNF-alpha Stimulates the Adhesion and Transendothelial Migration of Circulating Human CD14+ Monocytes That Develop With RANKL Into Functional Osteoclasts. J Bone Miner Res. 2006;21(2):193-206. PubMed PMID: 16418775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human microvascular endothelial cell activation by IL-1 and TNF-alpha stimulates the adhesion and transendothelial migration of circulating human CD14+ monocytes that develop with RANKL into functional osteoclasts. AU - Kindle,Libby, AU - Rothe,Linda, AU - Kriss,Michael, AU - Osdoby,Philip, AU - Collin-Osdoby,Patricia, Y1 - 2005/11/07/ PY - 2005/07/20/received PY - 2005/10/11/revised PY - 2005/11/02/accepted PY - 2006/1/19/pubmed PY - 2006/4/4/medline PY - 2006/1/19/entrez SP - 193 EP - 206 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 21 IS - 2 N2 - UNLABELLED: Circulating pre-OCs may be recruited to locally inflamed sites through specific interactions with activated microvasculature. We found that HMVECs stimulated the adhesion and TEM of circulating pre-OCs, in an ICAM-1- and CD44-dependent manner, leading to greater RANKL-induced OC formation and bone pit resorption. INTRODUCTION: Inflammation is critical for healing processes but causes severe tissue destruction when chronic. Local osteoclast (OC) formation and bone resorption may increase at inflammatory sites through multiple mechanisms, including direct stimulation by inflamed microvasculature of circulating OC precursor (pre-OC) migration through a blood vessel barrier into bone or joint tissue. How this might occur is not yet well understood. MATERIALS AND METHODS: Cytokine-activated human microvascular endothelial cell (HMVEC) monolayers, with or without IL-1 and TNF-alpha preactivation (24 h), were incubated in adhesion (1-3 h) or porous transwell transendothelial migration (TEM; 3 h) assays with human peripheral blood mononuclear cells (hPBMCs) or CD14+ monocyte or CD14- lymphocyte subsets. The number of cells that adhered or transmigrated, and their ability to thereafter develop with macrophage-colony stimulating factor (M-CSF) + RANKL into bone pit-resorbing OCs, were analyzed. Immunostaining and neutralizing antibodies to key cell adhesion molecules were used to determine their potential involvement in stimulated CD14+ monocyte TEM. RESULTS: M-CSF + RANKL caused OC and bone pit formation only from hPBMCs and CD14+ cells but not CD14- cells. Adhesion of hPBMCs or CD14+ cells but not CD14- cells was stimulated by cytokine preactivation of HMVECs and led to the full capture of all circulating pre-OCs capable of developing into OCs. Cytokine-preactivated HMVECs also promoted the postadhesion TEM of hPBMCs and CD14+ populations, resulting in markedly greater OC formation and bone pit resorption by transmigrated cells. Immunodetectable vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and CD44 levels increased on cytokine-treated HMVEC surfaces, and neutralizing antibodies to ICAM-1 or CD44, but not VCAM-1 or platelet endothelial cell adhesion molecule (PECAM-1), inhibited stimulated CD14+ cell TEM through activated HMVECs. CONCLUSIONS: This is the first demonstration that cytokine-activated HMVECs efficiently capture and promote the TEM of circulating pre-OCs capable of differentiating into bone-resorbing OCs. Thus, direct pre-OC recruitment by activated microvasculature at inflammatory sites may significantly contribute to normal OC bone remodeling during fracture healing or exacerbate pathological bone loss in various chronic inflammatory disorders. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/16418775/Human_microvascular_endothelial_cell_activation_by_IL_1_and_TNF_alpha_stimulates_the_adhesion_and_transendothelial_migration_of_circulating_human_CD14+_monocytes_that_develop_with_RANKL_into_functional_osteoclasts_ L2 - https://doi.org/10.1359/JBMR.051027 DB - PRIME DP - Unbound Medicine ER -