- 著者
- Namgil OH Sangho KIM Kenji HOSOYA Masahiro OKUMURA
- 出版者
- 公益社団法人 日本獣医学会
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.13-0482, (Released:2014-01-13)
- 被引用文献数
- 1 7
Suppressive effects of non-steroidal anti-inflammatory drugs (NSAIDs) on bone healing process have remained controversial, since no clinical data have clearly showed the relationship between NSAIDs and bone healing. The aim of this study was to assess compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib on osteogenic differentiation. Each of NSAIDs (10 µM) was treated during 20 days of osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes, which were up-regulated during continuous treatment of NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAIDs treatment.
- 著者
- Takafumi SUNAGA Namgil OH Kenji HOSOYA Satoshi TAKAGI Masahiro OKUMURA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- vol.74, no.6, pp.745-750, 2012 (Released:2012-07-04)
- 参考文献数
- 31
- 被引用文献数
- 1 3
Canine osteoarthritis occurs frequently and causes secondary synovitis. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the major therapeutic options for pain management of joint diseases. Tepoxalin has an unique property as an NSAIDs that suppresses both cyclooxygenase and lipoxygenase. The purpose of this study was to evaluate antiproliferative effects of tepoxalin on cultured canine synovial cells. Cytotoxic effects of tepoxalin, carprofen, meloxicam and AA-861 on cultured canine synoviocytes were evaluated by MTT colorimetric assay. Apoptosis was detected by morphological observations with Giemsa or annexin V/Hoechst 33342 staining and by the inhibition of caspase-3 activity with N-Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Cytotoxic effects of tepoxalin were evident in comparison with the effects of carprofen or meloxicam. The same tendency of cytotoxicity was observed when 5-lipoxygenase was inhibited by AA-861. The morphological findings and contradictory effects of Ac-DEVD-CHO with regard to the cytotoxicity proved the proapoptotic effects of tepoxalin. In conclusion, tepoxalin might control osteoarthritic synovitis by inducing apoptosis in proliferating synoviocytes, while most NSAIDs that selectively inhibit cyclooxygenase-2 most likely would not suppress synovial proliferation.
- 著者
- Takafumi SUNAGA Namgil OH Kenji HOSOYA Satoshi TAKAGI Masahiro OKUMURA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.1201080756, (Released:2012-01-12)
- 被引用文献数
- 1 3
Canine osteoarthritis occurs frequently and causes secondary synovitis. Administration of non-steroidal anti-inflammatory drugs (NSAIDs) is one of major therapeutic options for pain management of joint diseases. Tepoxalin has an unique property as NSAIDs, which suppress both cyclooxygenase and lipoxygenase. The purpose of this study was to evaluate anti-proliferative effects of tepoxalin on cultured canine synovial cells. Cytotoxic effects of tepoxalin, carprofen, meloxicam and AA-861 on cultured canine synoviocytes were evaluated by MTT colorimetric assay. Apoptosis was detected by morphological observations with giemsa or annexin-V/hoechst 33342 staining, and by the inhibition of caspase-3 activity with N-Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Cytotoxic effects of tepoxalin were evident in comparison with those of carprofen or meloxicam. Same tendency of the cytotoxicity was observed when 5-lipoxigenase was inhibited by AA-861. Morphological findings and contradictory effects of Ac-DEVD-CHO to the cytotoxicity proved pro-apoptotic effects of tepoxalin. In conclusion, tepoxalin might control osteoarthritic synovitis by inducing apoptosis on proliferated synoviocytes, while most NSAIDs with selective inhibition of cyclooxygenase-2 most likely would not suppress synovial proliferation.