Carbonic anhydrase inhibitors are antiarthritic in the rat

Nolan, Joseph C.; Gathright, C E; Radvany, Cynthia H.; Barrett, Richard J.; Sancilio, Lawrence F.

doi:10.1016/1043-6618(91)90042-v

Cited by 7 publications

(7 citation statements)

References 10 publications

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“…It has been found that carbonic anhydrase activity enhanced the stimulation of prostaglandin E 2 for bone resorption [12]. Some groups found that the carbonic anhydrase inhibitor acetazolamide inhibited bone resorption [30,31]. They suggested that the carbonic anhydrase inhibitors played an antiarthritic role by inhibiting bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible to ankylosing spondylitis

et al. 2012

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IntroductionAnkylosing spondylitis (AS) is characterized by abnormal bone formation in the spine and the sacroiliac joints. In vitro assays demonstrate that carbonic anhydrase I (CA1) promotes calcium precipitation. This study investigated the function of CA1 for bio-mineralization and determined if common polymorphisms in the CA1 gene might contribute to AS risk.MethodsCalcification was induced in Saos-2 cells, a human osteosarcoma cell line, with ascorbic acid and β-glycerophosphate. Calcification was determined by Alizarin Red-S (AR-S) staining. Expressions of CA1, alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN), osterix (OSX) and runt-related transcription factor-2 (Runx2) were determined by real-time PCR and western blotting. The cells were also treated with acetazolamide, an anti-carbonic anhydrase drug. Genotyping was performed using Illumina VeraCode microarray in a case-control study including 51 AS patients, 267 rheumatoid arthritis (RA) patients and 160 healthy controls. The result was confirmed by Taqman assay, including 258 AS patients, 288 RA patients and 288 healthy controls.ResultsFollowing the induction of calcification, Saos-2 cells produced large amounts of calcium-rich deposits. Increased transcriptions of CA1, ALP, BSP, OCN, OSX and Runx2, essential genes for ossification, were detected in the cultured cells. Following treatmen with acetazolamide, the expression of CA1 obviously declined and mineralized nodule formation was also decreased. Illumina microarray indicates that SNP at rs7841425 also showed significant differences in allelic frequency (P = 0.01396) and genotypic frequency (P = 0.005902) between AS cases and controls. In addition, SNP at rs7827474 showed significant differences in allelic frequency (P = 5.83E-04) and genotypic frequency (P = 0.000186) between RA cases and controls (P values were adjusted to multiple comparisons). The Taqman assay revealed that rs725605 demonstrated statistically significant evidence of allele frequency (P = 0.022307) and gene frequency (P = 0.007731) for association with AS. This SNP did not show significant differences in allelic frequencies and gene frequencies between RA patients and controls.ConclusionsCA1 may play an essential role in bio-mineralization and new bone formation. The gene encoding CA1 is susceptible to AS.

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Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible to ankylosing spondylitis

et al. 2012

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“…Nolan et al found that carbonic anhydrase inhibitors, including cetazolamide, ethoxzolamide, methazolamide and dichlorphenamide, reduced paw edema and attenuated the deterioration of the joints of rats with adjuvant arthritis. They suggested that the carbonic anhydrase inhibitors combat arthritis by inhibiting bone resorption 22. The increased bone resorption is a characteristic of AS 23, 24.…”

Section: Discussionmentioning

confidence: 99%

Treat Ankylosing Spondylitis with Methazolamide

Chang¹,

Yan²,

Zhang³

2011

Int. J. Med. Sci.

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Background: Increased bone resorption and new bone information are two characteristics of ankylosing spondylitis (AS). Much evidence has shown that carbonic anhydrase inhibitors can restrain bone resorption. We had detected increased expression of carbonic anhydrase I (CA1) in synovium of patients with AS. This study aimed to evaluate the effectiveness and safety of methazolamide, an anti-carbonic anhydrase drug, for treating patients with AS.Methods: Two patients, called as S and L, were diagnosed with active AS based on BASDAI and BASFI assessments, radiographic data and other clinical indices. They took methazolamide tablets at a dose of 25 mg twice every day.Results: Patient S's BASDAI score fell from 5.4 to 4.4, while patient L's BASDAI fell from 2.4 to 2. Patient S's BASFI score change from 2.7 to 2.9, while patient L's BASFI score fell from 1.2 to 0.2. The ESR values of patient S were considerably reduced, while the ESR value of patient L remained unchanged and in the normal range. The calcium concentration of patient S decreased from 3.05 mmol/L to 2.39 mmol/L. The CT evidence indicates that the articular surfaces of the erosive sacroiliac joints became clearer and the area of the calcium deposits began decreased. No significant systemic side effects were observed in either patient.Conclusions: The above results indicate that methazolamide was effective for active AS. Methazolamide may improve AS symptoms by inhibiting carbonic anhydrase activity during the processes of bone reporption and new bone formation.

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“…Nolan et al also found that carbonic anhydrase inhibitors including acetazolamide, ethoxzolamide, methazolamide, and dichlorphenamide reduced paw edema and attenuated joint deterioration in rats with adjuvant arthritis. They suggested that the carbonic anhydrase inhibitors played an antiarthritic role by inhibiting bone resorption [23]. These investigations demonstrated a functional role for carbonic anhydrase in the mediation of hormone-stimulated bone resorption [24].…”

Section: Discussionmentioning

confidence: 99%

Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing spondylitis

Chang

Han

Zhao

et al. 2010

BMC Musculoskelet Disord

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BackgroundOne of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation. Previous studies have indicated that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of AS. The present study used a proteomic approach to identify novel AS-specific proteins by simultaneously comparing the expression profiles of synovial membranes from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA).MethodsSynovial tissues were collected from the hip joints of patients with AS and knee joints of patients with RA or OA (n = 10 for each disease) during joint replacement surgery. Proteins extracted from the synovial tissues were separated by 2-D electrophoresis (2-DE), and the proteins with significantly increased expression in the AS samples were subjected to MALDI-TOF/TOF-MS analysis. The results were verified using western blotting and immunohistochemistry. Levels of the candidate proteins in synovial fluids from knee joints (n = 40 for each disease) were measured using ELISA.ResultsThe proteomic approach revealed significantly increased expression of carbonic anhydrase I (CA1) in the synovial membrane of patients with AS as compared with the RA and OA tissue samples. Immunohistochemistry and western blotting analysis confirmed the findings described above. The ELISA detected a higher level of CA1 in synovial fluids from patients with AS than those with OA. The mean value of the CA1 level was also higher in AS patients as compared with RA patients. This study also detected increased expression of alpha-1-antitrypsin in the synovial tissues from AS patients, which is in agreement with other reports.ConclusionIn vitro experiments by other groups indicated that CA1 catalyzes the generation of HCO3- through the hydration of CO2, which then combines with Ca2+ to form a CaCO3 precipitate. Calcification is an essential step of bone formation. Substantial evidence indicates that carbonic anhydrase also stimulates bone resorption. Hence, overexpression of CA1 in the synovial tissues of AS patients may promote improper calcification and bone resorption in AS.

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Carbonic anhydrase inhibitors are antiarthritic in the rat

Cited by 7 publications

References 10 publications

Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible to ankylosing spondylitis

Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible to ankylosing spondylitis

Treat Ankylosing Spondylitis with Methazolamide

Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing spondylitis

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