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RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production.
Bone. 2006 May; 38(5):678-85.BONE

Abstract

Receptor activator of NF-kappaB ligand (RANKL) and interleukin-1 (IL-1) individually plays a critical role in the differentiation and activation of osteoclasts in bone. In addition, both RANKL and IL-1 activate similar signal transduction pathways including p38 MAP kinase and c-Jun NH(2) terminal kinase (JNK). We examined if endogenously produced IL-1 influenced osteoclast-like cell (OCL) formation in murine bone marrow and bone marrow monocyte (BMM) cultures that were stimulated with M-CSF and RANKL. RANKL stimulated OCL formation in a dose-dependent manner in bone marrow cultures, and this response was significantly inhibited by IL-1 RA (100 ng/ml), a specific IL-1 antagonist. Interleukin-1 further increased OCL formation in BMM cultures that were treated with M-CSF (30 ng/ml) and RANKL (1, 3, 10 and 30 ng/ml). In addition, BMM cultures from IL-1 type I receptor-deficient mice, which do not respond to IL-1, demonstrated significantly less OCL formation compared to wild-type BMM cultures. We examined the time course and dose response of IL-1alpha protein expression by ELISA in BMM cultures that were treated with or without M-CSF and RANKL. RANKL dose dependently stimulated IL-1alpha protein significantly (up to 46%) in 6-day cultures. The interaction of RANKL and IL-1 on osteoclastogenesis did not appear significantly dependent on prostaglandin synthesis since PGE(2) expression in the conditioned medium of BMM cultures was nearly undetectable and the PGHS-2 specific inhibitor, NS-398, was without effect. We also investigated the effect of IL-1 on p38 MAP kinase and JNK in BMM cultures. The combination of RANKL and IL-1 had additive effects on JNK but not p38 MAP kinase compared to results in cultures treated with RANKL or IL-1 alone. In addition, SP600125, a specific JNK inhibitor, markedly reduced OCL formation in BMM cultures that were treated with RANKL or the combination of RANKL and IL-1. These findings demonstrate that endogenously produced IL-1 augments the response of bone marrow cells to RANKL, and this effect appears mediated by mechanisms that are associated with enhancement of JNK activity.

Authors+Show Affiliations

Division of Endocrinology, Department of Medicine, MC-1850, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1850, USA. slee@neuron.uchc.eduNo 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

16309985

Citation

Lee, Sun-Kyeong, et al. "RANKL-stimulated Osteoclast-like Cell Formation in Vitro Is Partially Dependent On Endogenous Interleukin-1 Production." Bone, vol. 38, no. 5, 2006, pp. 678-85.
Lee SK, Gardner AE, Kalinowski JF, et al. RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production. Bone. 2006;38(5):678-85.
Lee, S. K., Gardner, A. E., Kalinowski, J. F., Jastrzebski, S. L., & Lorenzo, J. A. (2006). RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production. Bone, 38(5), 678-85.
Lee SK, et al. RANKL-stimulated Osteoclast-like Cell Formation in Vitro Is Partially Dependent On Endogenous Interleukin-1 Production. Bone. 2006;38(5):678-85. PubMed PMID: 16309985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production. AU - Lee,Sun-Kyeong, AU - Gardner,Amy E, AU - Kalinowski,Judith F, AU - Jastrzebski,Sandra L, AU - Lorenzo,Joseph A, Y1 - 2005/11/23/ PY - 2005/07/06/received PY - 2005/09/30/revised PY - 2005/10/13/accepted PY - 2005/11/29/pubmed PY - 2006/7/29/medline PY - 2005/11/29/entrez SP - 678 EP - 85 JF - Bone JO - Bone VL - 38 IS - 5 N2 - Receptor activator of NF-kappaB ligand (RANKL) and interleukin-1 (IL-1) individually plays a critical role in the differentiation and activation of osteoclasts in bone. In addition, both RANKL and IL-1 activate similar signal transduction pathways including p38 MAP kinase and c-Jun NH(2) terminal kinase (JNK). We examined if endogenously produced IL-1 influenced osteoclast-like cell (OCL) formation in murine bone marrow and bone marrow monocyte (BMM) cultures that were stimulated with M-CSF and RANKL. RANKL stimulated OCL formation in a dose-dependent manner in bone marrow cultures, and this response was significantly inhibited by IL-1 RA (100 ng/ml), a specific IL-1 antagonist. Interleukin-1 further increased OCL formation in BMM cultures that were treated with M-CSF (30 ng/ml) and RANKL (1, 3, 10 and 30 ng/ml). In addition, BMM cultures from IL-1 type I receptor-deficient mice, which do not respond to IL-1, demonstrated significantly less OCL formation compared to wild-type BMM cultures. We examined the time course and dose response of IL-1alpha protein expression by ELISA in BMM cultures that were treated with or without M-CSF and RANKL. RANKL dose dependently stimulated IL-1alpha protein significantly (up to 46%) in 6-day cultures. The interaction of RANKL and IL-1 on osteoclastogenesis did not appear significantly dependent on prostaglandin synthesis since PGE(2) expression in the conditioned medium of BMM cultures was nearly undetectable and the PGHS-2 specific inhibitor, NS-398, was without effect. We also investigated the effect of IL-1 on p38 MAP kinase and JNK in BMM cultures. The combination of RANKL and IL-1 had additive effects on JNK but not p38 MAP kinase compared to results in cultures treated with RANKL or IL-1 alone. In addition, SP600125, a specific JNK inhibitor, markedly reduced OCL formation in BMM cultures that were treated with RANKL or the combination of RANKL and IL-1. These findings demonstrate that endogenously produced IL-1 augments the response of bone marrow cells to RANKL, and this effect appears mediated by mechanisms that are associated with enhancement of JNK activity. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/16309985/RANKL_stimulated_osteoclast_like_cell_formation_in_vitro_is_partially_dependent_on_endogenous_interleukin_1_production_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(05)00425-4 DB - PRIME DP - Unbound Medicine ER -