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Constitutive expression of parathyroid hormone‐related peptide PTHnP stimulates growth and inhibits differentiation of CFK2 chondrocytes
Author(s) -
Henderson Janet E.,
He Bin,
Goltzman David,
Karaplis Andrew C.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199610)169:1<33::aid-jcp4>3.0.co;2-f
Subject(s) - parathyroid hormone related protein , messenger rna , transfection , signal transduction , microbiology and biotechnology , chondrogenesis , cell culture , medicine , endocrinology , biology , chemistry , parathyroid hormone , gene , calcium , biochemistry , stem cell , genetics
We have examined the effects of constitutive expression of PTHrP on the growth and differentiation of populations of cells derived from a clonal chondrocytic cell line, CFK2. Cells were stably transfected with cDNA encoding either full‐length, secretory PTHrP (CFK2P) or nonsecretory PTHrP (CFK2P‐SS). In cultures of cells plated at low density, secretory PTHrP acted as a potent mitogen compared with nonsecretory PTHrP or exogenous PTHrP‐(1‐34), both of which stimulated only a minor increase in proliferation. In populations of control cells maintained postconfluent for several weeks, there was a dramatic increase in expression of mRNA for type II collagen, aggrecan, and link protein. Addition of exogenous PTHrP‐(1‐34) at a concentration of 10 −8 M to these cultures was ineffective in inhibiting this time‐dependent increase in expression of matrix proteins. In contrast, populations of cells producing either secretory or nonsecretory forms of PTHrP, maintained over the same time period, demonstrated an almost complete inhibition of mRNA expression for matrix proteins. These observations demonstrate that PTHrP acts as a bifunctional modulator of chondrogenesis and that some of its biological activity is exerted via a mechanism distinct from the recognised signal transduction pathways linked to the PTH/PTHrP receptor. © 1996 Wiley‐Liss, Inc.