著者

Satoshi TAKAGI Yumiko KAGAWA Kiwamu HANAZONO Shoko MURAKAMI Tatsuya DEGUCHI Yusuke IZUMI Kenji HOSOYA Sangho KIM 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.18-0148, (Released:2018-07-13)

被引用文献数

1

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A 10-year-old cat presented for evaluation with a 1-month history of salivation and oral bleeding. A right mandibular mass was palpated and computed tomography examination revealed entire bone proliferation. Mandibular bone biopsy was performed, and histopathological diagnosis was vascular hamartoma. The cat suddenly died on day 140.

著者

Yusuke IZUMI Yuki HOSHINO 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.14-0347, (Released:2014-12-05)

被引用文献数

1 2

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The present study involved the isolation and characterization of canine tumor endothelial cells (TECs) from two malignancies. TECs were isolated using magnetic cell sorting following FITC labeling with UEA1 lectin, and they were characterized by measuring genetic and histopathological endothelial markers. Isolated TECs exhibited a cobblestone-like morphology and expressed both vascular endothelial growth factor receptor 2 (VEGFR2) and Von Willebrand factor (vWF). Further, both TECs and tumor cells derived from a seminoma exhibited increased C-X-C chemokine receptor type 7 (CXCR7) expression. However, CXCR7 expression was not detected in TECs and tumor cells derived from a hepatocellular carcinoma. Understanding TEC specific traits may be important in the development of more efficacious anti-angiogenic therapies that do not induce adverse effects.

著者

Jun TAMURA Norihiko OYAMA So MATSUMOTO Ryo OWAKI Kenji HOSOYA 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.20-0446, (Released:2020-12-29)

被引用文献数

2

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Difficulty in airway management during anesthesia was noted in a 10-year-old, castrated, male Pekingese dog and a 13-year-old male French Bulldog. They showed strong resistance during tracheal tube insertion through the subglottic lumen. Therefore, the airway was secured by using a small endotracheal tube or supraglottic airway device. Computed tomography scan revealed a markedly narrower vertical dimension of the cricoid cartilage compared to that seen in common brachycephalic breeds. Posterior glottis was relatively more accessible for translaryngeal intubation in the present cases. Our findings showed that brachycephalic airway syndrome may be associated with narrow cricoid cartilage. To the best of our knowledge, this is the first clinical case report of airway management during anesthesia in dogs with narrow cricoid cartilage.

著者

Carol MWALE Takafumi SUNAGA Yanlin WANG Eugene C BWALYA H M Suranji WIJEKOON Sangho KIM 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.85, no.4, pp.515-522, 2023 (Released:2023-04-22)

参考文献数

42

被引用文献数

1

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Bupivacaine, levobupivacaine and ropivacaine are potent, long acting, amide-type local anesthetics that have several clinical applications including intra-articular administration. The objectives of this study were to evaluate their in vitro effects on cell viability and caspase activity to elucidate whether they activate the extrinsic or intrinsic pathways of apoptosis in canine articular chondrocytes. Chondrocytes in monolayer culture were treated with culture medium as the control, or with 0.062% (0.62 mg/mL) bupivacaine, 0.062% levobupivacaine, and 0.062% ropivacaine for 24 hr. Cell viability was evaluated using the live/dead, 3-(4,5-dimehylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), and Cell Counting Kit-8 (CCK-8) assays. Evaluation of caspase-3, caspase-8, and caspase-9 activity was performed using colorimetric assays. The MTT and CCK-8 assays were used to evaluate the effect of caspase inhibitors on local anesthetic chondrotoxicity. All three local anesthetics decreased chondrocyte viability after 24 hr (P<0.001). Apoptosis was induced through both the extrinsic and intrinsic pathways. Bupivacaine increased caspase-3, caspase-8, and caspase-9 activity (P<0.001). Levobupivacaine increased caspase-3 (P=0.03) while ropivacaine did not significantly upregulate activity for all three caspases. Caspase inhibition did not suppress bupivacaine chondrotoxicity whereas inhibition of caspase-8 and caspase-9 decreased ropivacaine chondrotoxicity and mildly attenuated levobupivacaine chondrotoxicity. In summary, the level of chondrotoxicity, the type of caspase activated, the level of caspase activation, and the response to caspase inhibitors was dependent on the type of local anesthetic. Therefore, ropivacaine may be a safer choice for intra-articular administration compared to levobupivacaine and bupivacaine.

著者

Ryo TAKEUCHI Satoshi TAKAGI Kenji HOSOYA Hiroshi OHTA Takaharu ITAMI 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.21-0384, (Released:2021-09-21)

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Canine gastroesophageal intussusception (GEI) is a rare and life-threatening condition that requires prompt diagnosis and treatment. A 19-day-old Siberian Husky with a 4-day history of regurgitation was diagnosed with GEI based on the findings of computed tomography (CT) performed without anesthesia. Endoscopic reduction of intussusception was impossible; thus, surgical reduction by traction of the duodenum was performed. CT revealed improvement of megaesophagus 82 days postoperatively. Eleven months postoperatively, fluoroscopy showed recovery to nearly normal esophageal motility. Two years postoperatively, no clinical signs were reported. CT is useful to diagnose GEI in neonate puppies with poor abdominal fat and to assess the gastric edema and the anatomical association of stomach with other organs. Fluoroscopy is helpful for evaluating postoperative esophageal motility.

著者

Ekkapol AKARAPHUTIPORN Eugene C. BWALYA Sangho KIM Takafumi SUNAGA Ryosuke ECHIGO 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.20-0091, (Released:2020-07-07)

被引用文献数

3

---

Pentosan polysulfate (PPS) is a semi-synthetic sulfated polysaccharide compound which has been shown the benefits on therapeutic treatment for osteoarthritis (OA) and has been proposed as a disease modifying osteoarthritis drugs (DMOADs). This study investigated the effects of PPS on cell proliferation, particularly in cell cycle modulation and phenotype promotion of canine articular chondrocytes (AC). Canine AC were treated with PPS (0–80 µg/ml) for 24, 48 and 72 hr. The effect of PPS on cell viability, cell proliferation and cell cycle distribution were analyzed by MTT assay, DNA quantification and flow cytometry. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) and glycosaminoglycan (GAG) quantification. PPS significantly reduced AC proliferation through cell cycle modulation particularly by maintaining a significantly higher proportion of chondrocytes in the G1 phase and a significantly lower proportion in the S phase of the cell cycle in a concentration- and time-dependent manner. While the proportion of chondrocytes in G1 phase corresponded with the significant downregulation of cyclin-dependent kinase (CDK) 1 and 4. Furthermore, the study confirms that PPS promotes a chondrogenic phenotype of AC through significant upregulation of collagen type II (Col2A1) mRNA and GAG synthesis. The effect of PPS on the inhibition of chondrocyte proliferation while promoting a chondrocyte phenotype could be beneficial in the early stages of OA treatment, which transient increase in proliferative activity of chondrocytes with subsequent phenotypic shift and less productive in an essential component of extracellular matrix (ECM) is observed.

著者

Ekkapol AKARAPHUTIPORN Takafumi SUNAGA Eugene C. BWALYA Ryosuke ECHIGO 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.20-0118, (Released:2020-04-30)

被引用文献数

3

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This study investigated the effects of culture time on phenotype stability of canine articular chondrocytes (CACs) in non-passaged long-term monolayer culture. Third passage (P3) CACs isolated from four cartilage samples were seeded at three different initial seeding densities (0.2 х 104, 1.0 х 104 and 5.0 х 104 cells/cm2) and maintained in monolayer condition up to 8 weeks without undergoing subculture after confluence. The characteristic changes of chondrocytes during the culture period were evaluated based on the cell morphology, cell proliferation, glycosaminoglycans (GAGs) content, DNA quantification, mRNA expression and ultrastructure of chondrocytes. Chondrocytes maintained under post-confluence condition exhibited a capability to grow and proliferate up to 4 weeks. Alcian blue staining and Dimethylmethylene blue (DMMB) assay revealed that the extracellular matrix (ECM) synthesis was increased in a time-dependent manner from 2 to 8 weeks. The chondrocyte mRNA expression profile was dramatically affected by prolonged culture time, with a significant downregulation of collagen type I, whereas the expression of collagen type II, aggrecan, Sox9 and matrix metalloproteinase 13 (MMP-13) were significantly upregulated. In addition, transmission electron microscopy (TEM) result indicated dilation of rough endoplasmic reticulum (RER) in these long-term monolayer cultured chondrocytes. These findings demonstrate that the chondrocytes phenotype could be partially redifferentiated through the spontaneous redifferentiation process in long-term cultures using standard culture medium without the addition of chondrogenic supplements or tissue-culture scaffolds.

著者

Satoshi TAKAGI Yumiko KAGAWA Kiwamu HANAZONO Shoko MURAKAMI Tatsuya DEGUCHI Yusuke IZUMI Kenji HOSOYA Sangho KIM 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.80, no.9, pp.1456-1458, 2018 (Released:2018-09-26)

参考文献数

18

被引用文献数

1

---

A 10-year-old cat presented for evaluation with a 1-month history of salivation and oral bleeding. A right mandibular mass was palpated and computed tomography examination revealed entire bone proliferation. Mandibular bone biopsy was performed, and histopathological diagnosis was vascular hamartoma. The cat suddenly died on day 140.

著者

Eugene C. BWALYA HM Suranji WIJEKOON Jing FANG Sangho KIM Kenji HOSOYA 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.18-0202, (Released:2018-09-11)

被引用文献数

1

---

Although chondroinductive growth factors are considered necessary for chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSC), independent and spontaneous chondrogenesis has been previously demonstrated in adult horses, bovine calves and adult human BMSC. Surprisingly, adult canine BMSC under similar culture conditions previously failed to demonstrate chondrogenesis. The present study evaluated independent chondrogenic potential of BMSC sourced from three young dogs in the absence of known chondroinductive factors. BMSC were culture expanded in 10% DMEM up to third passage (P3). At each passage, the phenotype of BMSC was evaluated by RT-PCR gel electrophoresis and qPCR. BMSC exhibited a chondrogenic phenotype in the absence of dexamethasone and TGF-β1 as verified by the expression of Sox-9, type II collagen and aggrecan. Sox-9 was significantly downregulated (P<0.05) from P1–P3 compared to P0 while type II and X collagen, and aggrecan were significantly downregulated at P3 compared to P0. There was a significant (P<0.01) negative correlation between passaging and Sox-9, type II collagen and aggrecan gene expression. These results indicate that independent chondrogenic potential and phenotype retention of BMSC decreases in a passage-dependent pattern. Therefore, caution should be exercised for future experiments evaluating the chondrogenic potential of BMSC after extensive expansion cultures in 10% DMEM.

著者

Suranji WIJEKOON Eugene C. BWALYA Jing FANG 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.17-0393, (Released:2017-11-03)

被引用文献数

6

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The aim of this study was to investigate osteoclastogenic properties of inflammatory cytokines at different time-points of osteoclastogenesis. Bone marrow-derived macrophages from five healthy dogs were stimulated with the macrophage colony-stimulating factor, receptor activator of nuclear factor-κB ligand and inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-17. Osteoclasts (OC) formation and function were enhanced with TNF-α regardless of temporal differences. But in contrast, IL-1β suppressed the osteoclastogenesis at early phase of the process while upregulating at the late phase. Furthermore, differentiation of OC precursors into OC was suppressed at high concentrations of IL-17. Collectively, the results revealed that suppressing TNF-α would be a promising strategy to inhibit inflammation-associated bone destruction in dogs.

著者

Eugene C. BWALYA Sangho KIM Jing FANG H. M. Suranji WIJEKOON 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

vol.79, no.7, pp.1182-1190, 2017 (Released:2017-07-07)

参考文献数

44

被引用文献数

11

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Mesenchymal stem cells (MSC) are a potential alternative source of differentiated chondrocytes for cartilage tissue regeneration and repair of osteoarthritic (OA) joints. We investigated the effects of pentosan polysulfate (PPS) and polysulfated glycosaminoglycan (PSGAG) on chondrogenesis of canine bone marrow-derived mesenchymal stem cells (cBMSC) in alginate and micromass cultures (MMC). Chondrogenic differentiation medium (CDM) was supplemented with PPS or PSGAG at concentrations of 0 (positive control; PC), 1, 3 and 5 µg/ml. 10% DMEM was used as negative control. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) for alginate cultures and Alcian blue staining for proteoglycan (PG) synthesis for MMC. In alginate culture, PPS and PSGAG showed no significant effect on type II collagen, aggrecan and HIF-2α mRNA expression. PPS had no significant effect on type I collagen whereas PSGAG significantly upregulated (P<0.05) it at all concentrations relative to other treatments. PPS demonstrated a dose-dependent inhibitory effect on type X collagen mRNA with significant inhibition observed at 5 µg/ml compared to the NC. PSGAG showed an inverse effect on type X collagen with 1 µg/ml significantly inhibiting its expression while increase in the concentration correspondingly increased type X collagen expression. In MMC, PPS significantly enhanced chondrogenesis and PG deposition whereas PSGAG inhibited chondrogenesis and promoted a fibrocartilage-like phenotype with reduced PG deposition. While PPS enhances chondrogenesis of cBMSC in MMC, the response of MSC to chondroinductive factors is culture system-dependent and varies significantly between alginate and MMC.

著者

Eugene C. BWALYA Sangho KIM Jing FANG H.M. Suranji WIJEKOON 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.17-0084, (Released:2017-05-27)

被引用文献数

11

---

Mesenchymal stem cells (MSC) are a potential alternative source of differentiated chondrocytes for cartilage tissue regeneration and repair of osteoarthritic (OA) joints. We investigated the effects of pentosan polysulfate (PPS) and polysulfated glycosaminoglycan (PSGAG) on chondrogenesis of canine bone marrow-derived mesenchymal stem cells (cBMSC) in alginate and micromass cultures (MMC). Chondrogenic differentiation medium (CDM) was supplemented with PPS or PSGAG at concentrations of 0 (positive control; PC), 1, 3 and 5 μg/ml. 10% DMEM was used as negative control. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) for alginate cultures and Alcian blue staining for proteoglycan (PG) synthesis for MMC. In alginate culture, PPS and PSGAG showed no significant effect on type II collagen, aggrecan and HIF-2α mRNA expression. PPS had no significant effect on type I collagen whereas PSGAG significantly upregulated (P<0.05) it at all concentrations relative to other treatments. PPS demonstrated a dose-dependent inhibitory effect on type X collagen mRNA with significant inhibition observed at 5 μg/ml compared to the NC. PSGAG showed an inverse effect on type X collagen with 1 μg/ml significantly inhibiting its expression while increase in the concentration correspondingly increased type X collagen expression. In MMC, PPS significantly enhanced chondrogenesis and PG deposition whereas PSGAG inhibited chondrogenesis and promoted a fibrocartilage-like phenotype with reduced PG deposition. While PPS enhances chondrogenesis of cBMSC in MMC, the response of MSC to chondroinductive factors is culture system-dependent and varies significantly between alginate and MMC.

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

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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

Kazuya EDAMURA Jonathan N. KING Wolfgang SEEWALD Nobuhiro SAKAKIBARA 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

vol.74, no.9, pp.1121-1131, 2012 (Released:2012-10-01)

参考文献数

23

被引用文献数

5 18 10

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The efficacy and tolerability of robenacoxib for the treatment of osteoarthritis in dogs were evaluated in a prospective, multicenter, randomized, noninferiority design clinical trial. A total of 32 dogs presenting with osteoarthritis were allocated randomly to receive, orally once daily for 28 days, either 1–2 mg/kg robenacoxib (n=21) or 3.5–5 mg/kg carprofen (n=11). Dogs were assessed by clinicians and owners using numerical rating scale scores at baseline and days 14 and 28. The primary efficacy endpoint was the global functional disability score, which was the sum of clinician scores for standing posture, lameness at walk, lameness at trot, willingness to raise the contralateral limb and pain at palpation. There was a good to excellent level of efficacy in both treatment groups. Differences between days 14 and 28 compared to day 0 were significant for all 11 clinician and owner scores for robenacoxib, and for 6 of 11 scores for carprofen. The efficacy of robenacoxib was numerically superior to carprofen for all 13 endpoints, but differences were not statistically significant. For the global functional disability score, the estimated efficacy of robenacoxib was 1.244 (95% confidence interval 0.555–2.493) relative to carprofen. The tolerability of both treatments was good as assessed from adverse events, clinical signs, and hematology and serum biochemistry variables. In conclusion, once daily administration of robenacoxib tablets had noninferior efficacy and tolerability compared to carprofen for the treatment of the clinical signs of osteoarthritis in dogs.

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

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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

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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.