Thrombin, but not bradykinin, stimulates proliferation in isolated human osteoblasts, via a mechanism not dependent on endogenous prostaglandin formation.
Osteolysis or osteosclerosis often occurs in bone tissue adjacent to chronic inflammatory processes. Numerous cytokines and inflammatory mediators have been implicated as osteoclast-activating agents, explaining inflammation-induced bone resorption. In many cases, the cause of the sclerosis seen in these lesions is less thoroughly investigated. We have studied the effects of thrombin and bradykinin, 2 inflammatory mediators, on the rate of proliferation in isolated human osteoblasts (hOBs). Thrombin, at and above 1 U/mL, stimulated the rate of thymidine incorporation into hOBs. The absolute cell number also increased, as measured by an assay based on the detection of cell metabolism. A synthetic peptide ligand for the thrombin receptor enhanced the rate of [3H]thymidine incorporation in hOBs, indicating that thrombin-induced proliferation is mediated via the tetheric thrombin receptor. The thrombin-induced proliferation was not affected by indomethacin, excluding prostanoids as mediators of this effect. Bradykinin did not affect either the rate of thymidine incorporation, or number of cells in long-term cultures of hOBs. In conclusion, the inflammatory mediator, thrombin, stimulates proliferation in isolated human osteoblasts probably via the recently described G-protein-coupled tetheric thrombin receptor. Thrombin may therefore be involved as a mediator of inflammation-induced sclerosis and bone formation.
Frost
A
A
Department of Surgical Sciences, University of Uppsala, Sweden. anders.frost@ortopedi.uu.se
Jonsson
K B
KB
Ridefelt
P
P
Nilsson
O
O
Ljunghall
S
S
Ljunggren
O
O
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000494:pharmacology; D001920:Bradykinin / Q000276:immunology* / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D002908:Chronic Disease; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007213:Indomethacin / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D010014:Osteolysis / Q000276:immunology*; D010026:Osteosclerosis / Q000276:immunology*; D011453:Prostaglandins / Q000096:biosynthesis*; D018002:Receptors, Bradykinin / Q000032:analysis; D018179:Receptors, Thrombin / Q000032:analysis; D013917:Thrombin / Q000276:immunology* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D018002:Receptors, Bradykinin; D018179:Receptors, Thrombin; D004247:DNA; D013917:Thrombin; D001920:Bradykinin; D007213:Indomethacin