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Implications of minocycline, platelet-derived growth factor, and transforming growth factor-beta on inflammatory
1Department of Periodontology, Guy's King's & St. Thomas' Dental Institute, King's College, London, UK.
Background:
Semisynthetic tetracyclines used in the adjunctive treatment of inflammatory periodontal disease enhance collagen expression in induced periodontal lesions of rats. Polypeptide growth factors regulate key cellular events in tissue repair. The physiologically active androgen 5 alpha-dihydrotestosterone (DHT) stimulates bone and connective tissue turnover. It was relevant to study the effects of transforming growth factor beta (TGF-beta)/platelet-derived growth factor (PDGF) and minocycline alone and in combination on the formation of biologically effective androgens which can influence repair.
Methods:
Confluent monolayer cultures of human gingival fibroblasts of the fifth through the ninth passage were incubated in Eagle's minimum essential medium, with 14C-testosterone/14C-4-androstenedione in the presence or absence of optimal concentrations of TGF-beta/PDGF/minocycline (M), alone and in combination. At the end of a 24-hour incubation period, the medium was analyzed for steroid metabolites and quantified using a radioisotope scanner.
Results:
The androgen substrates 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) were metabolized to DHT and 4-androstenedione/testosterone respectively. There were significant increases in the formation of DHT from 14C-T in response to M, TGF-beta, and PDGF, alone and in combination (13 to 48%), compared with controls (n = 4; P<0.01). The yields of 4-androstenedione were also greater in response to these agents (31%; 3-fold). When 14C-4-A was used as substrate, there were 21 to 80% increases in the formation of DHT in response to these agents alone and in combination (n = 4; P<0.01).
Conclusions:
The biologically effective androgen metabolites formed in response to minocycline, TGF-beta, and PDGF can contribute to reparatory events in the inflamed periodontium. Judicious, adjunctive usage of the chemically-modified tetracyclines in the treatment of periodontal diseases can obviate the risk of microbial resistance, with potential applications of their anti-inflammatory and proanabolic effects in regenerative technology.