The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without activating phospholipase C |
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Authors: | Guo Jun Chung Ung-Il Kondo Hisatomo Bringhurst F Richard Kronenberg Henry M |
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Institution: | Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA. |
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Abstract: | One G protein-coupled receptor (GPCR) can activate more than one G protein, but the physiologic importance of such activation has not been demonstrated in vivo. We have generated mice expressing exclusively a mutant form of the PTH/PTHrP receptor (DSEL) that activates adenylyl cyclase normally but not phospholipase C (PLC). DSEL mutant mice exhibit abnormalities in embryonic endochondral bone development, including delayed ossification and increased chondrocyte proliferation. Analysis of the differentiation of embryonic metatarsals in vitro shows that PTH(1-34) and forskolin inhibit, whereas active phorbol ester stimulates, hypertrophic differentiation. Thus, PLC signaling via the PTH/PTHrP receptor normally slows the proliferation and hastens the differentiation of chondrocytes, actions that oppose the dominant effects of PTH/PTHrP receptors and that involve cAMP-dependent signaling pathways. |
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