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Endocrinology Vol. 140, No. 12 5883-5893
Copyright © 1999 by The Endocrine Society

ARTICLES

Expression and Signal Transduction of Calcium-Sensing Receptors in Cartilage and Bone1

Wenhan Chang, Chialing Tu, Tsui-Hua Chen, Laszlo Komuves, Yuko Oda, Stacy A. Pratt, Scott Miller and Dolores Shoback

Endocrine Research Unit (W.C., C.T., T.-H.C., S.A.P., D.S.), Department of Medicine, Department of Dermatology (L.K., Y.O.), Veterans Affairs Medical Center, University of California, San Francisco, California 94121; and Department of Radiobiology (S.M.), School of Medicine, University of Utah, Salt Lake City, Utah 84112

Address all correspondence and requests for reprints to: Dolores Shoback, 111N, Endocrine Research Unit, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California 94121. E-mail: dolores{at}itsa.ucsf.edu

We previously showed that Ca2+-sensing receptors (CaRs) are expressed in chondrogenic RCJ3.1C5.18 (C5.18) cells and that changes in extracellular [Ca2+] ([Ca2+]o) modulate nodule formation and chondrogenic gene expression. In the present study, we detected expression of CaRs in mouse, rat, and bovine cartilage and bone by in situ hybridization, immunocytochemistry, immunoblotting, and RT-PCR; and we tested the effects of CaR agonists on signal transduction in chondrogenic and osteogenic cell lines. In situ hybridization detected CaR transcripts in most articular chondrocytes and in the hypertrophic chondrocytes of the epiphyseal growth plate. Expression of CaR transcripts was weak or absent, however, in proliferating and maturing chondrocytes in the growth plate. In bone, CaR transcripts were present in osteoblasts, osteocytes, and bone marrow cells, but rarely in osteoclasts. A complementary DNA was amplified from mouse growth plate cartilage, which was highly homologous to the human parathyroid CaR sequence. Immunocytochemistry of cartilage and bone with CaR antisera confirmed these findings. Western blotting revealed specific bands (~140–190 kDa) in membrane fractions isolated from growth plate cartilage, primary cultures of rat chondrocytes, and several osteogenic cell lines (SaOS-2, UMR-106, ROS 17/2.8, and MC3T3-E1). InsP responses to high [Ca2+]o were evident in C5.18 cells and all osteogenic cell lines tested except for SaOS-2 cells. In the latter, high [Ca2+]o reduced PTH-induced cAMP formation. Raising [Ca2+]o also increased intracellular free [Ca2+] in SaOS-2 and C5.18 cells. These studies confirm expression of CaRs in cartilage and bone and support the concept that changes in [Ca2+]o may couple to signaling pathways important in skeletal metabolism.




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