Age-related changes in gap junctional intercellular communication in osteoblastic cells.
Aging demonstrates deleterious effects upon the skeleton which can predispose an individual to osteoporosis and related fractures. Despite the well-documented evidence that aging decreases bone formation, there remains little understanding whereby cellular aging alters skeletal homeostasis. We, and others, have previously demonstrated that gap junctions--membrane-spanning channels that allow direct cell-to-cell conductance of small signaling molecules--are critically involved in osteoblast differentiation and skeletal homeostasis. We examined whether the capacity of rat osteoblastic cells to form gap junctions and respond to known modulators of gap junction intercellular communication (GJIC) was dependent on the age of the animal from which they were isolated. We observed no effect of age upon osteoblastic Cx43 mRNA, protein or GJIC. We also examined age-related changes in PTH-stimulated GJIC. PTH demonstrated age-dependent effects upon GJIC: Osteoblastic cells from young rats increased GJIC in response to PTH, whereas there was no change in GJIC in response to PTH in osteoblastic cells from mature or old rats. PTH-stimulated GJIC occurred independently of changes in Cx43 mRNA or protein expression. Cholera toxin significantly increased GJIC in osteoblastic cells from young rats compared to those from mature and old rats. These data demonstrate an age-related impairment in the capacity of osteoblastic cells to generate functional gap junctions in response to PTH, and suggest that an age-related defect in G protein-coupled adenylate cyclase activity at least partially contributes to decreased PTH-stimulated GJIC.
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Damian C
DC
Genetos
Zhiyi
Z
Zhou
Zhongyong
Z
Li
Henry J
HJ
Donahue
D000367:Age Factors; D000375:Aging; D000818:Animals; D002450:Cell Communication; D002772:Cholera Toxin / Q000494:pharmacology; D018031:Connexin 43 / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D006706:Homeostasis; D008297:Male; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D018031:Connexin 43; D012333:RNA, Messenger; D002772:Cholera Toxin; D000242:Cyclic AMP