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Intermittent PTH(1-34) signals through protein kinase A to regulate osteoprotegerin production in human periodontal ligament cells in vitro.

Abstract：

:Periodontal ligament (PDL) cells have been associated with the regulation of periodontal repair processes by the differential expression of osteoprotegerin and RANKL in response to intermittent parathyroid hormone (PTH) resulting in a modified activity of bone-resorbing osteoclasts. Here, we examined the intracellular signaling pathways that PDL cells use to mediate the PTH(1-34) effect on osteoprotegerin production and hypothesized that those would be dependent on the cellular maturation stage. Two stages of confluence served as a model for cellular maturation of 5th passage human PDL cells from six donors. Intermittent PTH(1-34) (10(-12) M) and PTH(1-31), the latter lacking the protein kinase C (PKC) activating domain, induced a significant decrease of osteoprotegerin production in confluent cultures, whereas the signal-specific fragments PTH(3-34) and PTH(7-34), which both are unable to activate protein kinase A (PKA), had no effect. The addition of the PKA inhibitor H8 antagonized the PTH(1-34) effect, whereas the PKC inhibitor RO-32-0432 did not. In pre-confluent, less mature cultures, intermittent PTH(1-34) resulted in a significant increase of osteoprotegerin. Similar results were obtained when PTH(1-31) substituted for PTH(1-34) as opposed to a lack of an effect of PTH(3-34) and PTH(7-34). Likewise, in confluent cultures, H8 inhibited the PTH(1-34) effect in pre-confluent cultures contrasted by RO-32-0432 which had no effect. These findings indicate that PTH(1-34) signaling targeting osteoprotegerin production in PDL cells involves a PKA-dependent pathway. The PTH(1-34) effect is dependent on cell status, whereas intracellular signal transduction is not. Clinical trials will have to prove whether those in vitro data are of physiological relevance for interference strategies.

journal_name

Clin Oral Investig

journal_title

Clinical oral investigations

authors

Kraus D,Jäger A,Abuduwali N,Deschner J,Lossdörfer S

doi

10.1007/s00784-011-0541-z

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

611-8

issue

eissn

1432-6981

issn

1436-3771

journal_volume

pub_type

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Intermittent PTH(1-34) signals through protein kinase A to regulate osteoprotegerin production in human periodontal ligament cells in vitro.