L C Tetlow1, D E Woolley. 1. University Department of Medicine, Manchester Royal Infirmary, Oxford Road, UK. lynne.c.tetlow@man.ac.uk
Abstract
OBJECTIVES: To determine the effects of histamine on matrix metalloproteinase (MMP) production by human articular chondrocytes (HAC) in vitro. METHODS: Conditioned culture medium from HAC cultures incubated with and without 20 microM histamine was assayed by enzymne linked immunosorbent assay (ELISA) for MMP-1, MMP-8, MMP-13 (collagenases 1, 2, and 3, respectively) and MMP-3 (stromelysin). Monolayer cultures of HAC were also immunostained for MMP-13 and MMP-3. RESULTS: The HAC cultures showed a significant increase in MMP-13 and MMP-3 production (2.2- and 1.9-fold, respectively) after treatment with 20 microM histamine for 24 hours, but MMP-1 and MMP-8 were unaffected. All cultures showed MMP-13 and MMP-3 detectable by immunolocalisation. MMP-3 was the more prominent enzyme as shown by both ELISA and immunolocalisation techniques. CONCLUSIONS: Histamine exposure increased both MMP-13 and MMP-3 production by HAC in vitro, thereby suggesting a pathophysiological role in the chondrocytic phenotype associated with degenerative changes in osteoarthritis.
OBJECTIVES: To determine the effects of histamine on matrix metalloproteinase (MMP) production by human articular chondrocytes (HAC) in vitro. METHODS: Conditioned culture medium from HAC cultures incubated with and without 20 microM histamine was assayed by enzymne linked immunosorbent assay (ELISA) for MMP-1, MMP-8, MMP-13 (collagenases 1, 2, and 3, respectively) and MMP-3 (stromelysin). Monolayer cultures of HAC were also immunostained for MMP-13 and MMP-3. RESULTS: The HAC cultures showed a significant increase in MMP-13 and MMP-3 production (2.2- and 1.9-fold, respectively) after treatment with 20 microM histamine for 24 hours, but MMP-1 and MMP-8 were unaffected. All cultures showed MMP-13 and MMP-3 detectable by immunolocalisation. MMP-3 was the more prominent enzyme as shown by both ELISA and immunolocalisation techniques. CONCLUSIONS:Histamine exposure increased both MMP-13 and MMP-3 production by HAC in vitro, thereby suggesting a pathophysiological role in the chondrocytic phenotype associated with degenerative changes in osteoarthritis.
Authors: Wilhelmiina Hämäläinen; Juha Savinainen; Petteri Nieminen; Marko Lehtonen; Saara Lehtiniemi; Juho Rinta-Paavola; Petri Lehenkari; Tommi Kääriäinen; Antti Joukainen; Heikki Kröger; Tommi Paakkonen; Anne-Mari Mustonen Journal: Inflammation Date: 2022-01-18 Impact factor: 4.657