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Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts.
J Clin Invest 2006; 116(12):3150-9JCI

Abstract

Genomic actions induced by 1alpha25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are crucial for normal bone metabolism, mainly because they regulate active intestinal calcium transport. To evaluate whether the vitamin D receptor (VDR) has a specific role in growth-plate development and endochondral bone formation, we investigated mice with conditional inactivation of VDR in chondrocytes. Growth-plate chondrocyte development was not affected by the lack of VDR. Yet vascular invasion was impaired, and osteoclast number was reduced in juvenile mice, resulting in increased trabecular bone mass. In vitro experiments confirmed that VDR signaling in chondrocytes directly regulated osteoclastogenesis by inducing receptor activator of NF-kappaB ligand (RANKL) expression. Remarkably, mineral homeostasis was also affected in chondrocyte-specific VDR-null mice, as serum phosphate and 1,25(OH)(2)D levels were increased in young mice, in whom growth-plate activity is important. Both in vivo and in vitro analysis indicated that VDR inactivation in chondrocytes reduced the expression of FGF23 by osteoblasts and consequently led to increased renal expression of 1alpha-hydroxylase and of sodium phosphate cotransporter type IIa. Taken together, our findings provide evidence that VDR signaling in chondrocytes is required for timely osteoclast formation during bone development and for the endocrine action of bone in phosphate homeostasis.

Authors+Show Affiliations

Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17099775

Citation

Masuyama, Ritsuko, et al. "Vitamin D Receptor in Chondrocytes Promotes Osteoclastogenesis and Regulates FGF23 Production in Osteoblasts." The Journal of Clinical Investigation, vol. 116, no. 12, 2006, pp. 3150-9.
Masuyama R, Stockmans I, Torrekens S, et al. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. J Clin Invest. 2006;116(12):3150-9.
Masuyama, R., Stockmans, I., Torrekens, S., Van Looveren, R., Maes, C., Carmeliet, P., ... Carmeliet, G. (2006). Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. The Journal of Clinical Investigation, 116(12), pp. 3150-9.
Masuyama R, et al. Vitamin D Receptor in Chondrocytes Promotes Osteoclastogenesis and Regulates FGF23 Production in Osteoblasts. J Clin Invest. 2006;116(12):3150-9. PubMed PMID: 17099775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. AU - Masuyama,Ritsuko, AU - Stockmans,Ingrid, AU - Torrekens,Sophie, AU - Van Looveren,Riet, AU - Maes,Christa, AU - Carmeliet,Peter, AU - Bouillon,Roger, AU - Carmeliet,Geert, Y1 - 2006/11/09/ PY - 2006/06/21/received PY - 2006/09/19/accepted PY - 2006/11/14/pubmed PY - 2007/1/24/medline PY - 2006/11/14/entrez SP - 3150 EP - 9 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 116 IS - 12 N2 - Genomic actions induced by 1alpha25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are crucial for normal bone metabolism, mainly because they regulate active intestinal calcium transport. To evaluate whether the vitamin D receptor (VDR) has a specific role in growth-plate development and endochondral bone formation, we investigated mice with conditional inactivation of VDR in chondrocytes. Growth-plate chondrocyte development was not affected by the lack of VDR. Yet vascular invasion was impaired, and osteoclast number was reduced in juvenile mice, resulting in increased trabecular bone mass. In vitro experiments confirmed that VDR signaling in chondrocytes directly regulated osteoclastogenesis by inducing receptor activator of NF-kappaB ligand (RANKL) expression. Remarkably, mineral homeostasis was also affected in chondrocyte-specific VDR-null mice, as serum phosphate and 1,25(OH)(2)D levels were increased in young mice, in whom growth-plate activity is important. Both in vivo and in vitro analysis indicated that VDR inactivation in chondrocytes reduced the expression of FGF23 by osteoblasts and consequently led to increased renal expression of 1alpha-hydroxylase and of sodium phosphate cotransporter type IIa. Taken together, our findings provide evidence that VDR signaling in chondrocytes is required for timely osteoclast formation during bone development and for the endocrine action of bone in phosphate homeostasis. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/17099775/Vitamin_D_receptor_in_chondrocytes_promotes_osteoclastogenesis_and_regulates_FGF23_production_in_osteoblasts_ L2 - https://doi.org/10.1172/JCI29463 DB - PRIME DP - Unbound Medicine ER -