Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders

Hegemann, Nina; Kohn, Barbara; Brunnberg, Leo; Schmidt, Michael F. G.

doi:10.1053/joca.2002.0820

Cited by 51 publications

(50 citation statements)

References 34 publications

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“…Tissue levels of TIMP-1 during bacterial infections have not been determined yet, but from other types of inflammation (14) we can estimate them to be around 500 ng/ml or higher.…”

Section: Discussionmentioning

confidence: 94%

Tissue Inhibitor of Metalloproteinase 1 Activates Normal Human Granulocytes, Protects Them from Apoptosis, and Blocks Their Transmigration during Inflammation

et al. 2004

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Urinary levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) higher than those of matrix metalloproteinase 9 (MMP-9) during acute pyelonephritis have previously been associated with a higher degree of acute inflammation and of postinfective renal scarring. The aim of the present study was to evaluate possible mechanisms by which TIMP-1 could affect the scarring process already during the acute phase of inflammation. The growth of Escherichia coli, bactericidal activity of fresh human blood, and respiratory burst, spontaneous apoptosis, and trans-basement membrane migration of normal human granulocytes were studied in vitro in the presence of different concentrations of recombinant human TIMP-1. To imitate the "normal" environment during inflammation in the kidney, granulocytes were also incubated with a conditioned medium from E. coli-stimulated renal epithelial cells. In order to compare our data with the in vivo situation, blood and urinary leukocyte levels were analyzed for 40 children with acute pyelonephritis, together with urinary MMP-9 and TIMP-1 levels. TIMP-1 at a concentration of 500 ng/ml increased the bactericidal activity of blood, increased the respiratory burst of granulocytes, decreased phosphatidylserine exposure and caspase 3 activity, which are features of spontaneous apoptosis, and inhibited granulocyte transmigration. Moreover, in the patients with pyelonephritis, MMP-9/TIMP-1 ratios in urine correlated with the degree of leukocyte transmigration. Thus, our data suggest that TIMP-1 specifically blocks the transmigration of granulocytes into urine. Entrapped and activated granulocytes, protected from apoptosis, might excessively destroy renal parenchyma and thus contribute to the pathogenesis of renal scarring following acute pyelonephritis.

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“…Tissue levels of TIMP-1 during bacterial infections have not been determined yet, but from other types of inflammation (14) we can estimate them to be around 500 ng/ml or higher.…”

Section: Discussionmentioning

confidence: 94%

Tissue Inhibitor of Metalloproteinase 1 Activates Normal Human Granulocytes, Protects Them from Apoptosis, and Blocks Their Transmigration during Inflammation

et al. 2004

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“…Therefore, various studies have focused on identifying a biomarker which is mostly macromolecule or fragment released from the joint tissue, as indicators of normal biological process and pathogenic process in the serum or synovial fluid. They have made numerous attempts to apply this concept for diagnosing the early stage of OA, monitoring the treatment response and determining the prognosis of OA (Malemud and Goldberg, 1999;Hegemann et al, 2002;Budsberg et al, 2006).…”

mentioning

confidence: 99%

Tartrate-resistant acid phosphatase, matrix metalloproteinase-2 and tissue inhibitor metalloproteinase-2 in early stages of canine osteoarthritis

Lee¹,

Alam²,

Seol³

et al. 2008

Vet. Med. - Czech

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ABSTRACT:The aim of this study was to determine if the activity of tartrate-resistant acid phosphatase (TRAP) in the synovial fluid (SF) and serum can be used as a marker for diagnosing the early stages of osteoarthritis (OA). We also wished to determine if identifiable differences in the concentrations of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) could be detected in SF between normal joints and OA joints for the diagnosis of early OA. Ten skeletally mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and medial meniscectomy. Five sham-operated beagle dogs were used as controls. The synovial fluid was collected in 1, 2 and 3 months and examined by western blotting for MMP-2 and ELISA for TIMP-2. The activity of TRAP in the SF and serum was measured using a spectrophotometer. In addition, the presence of TRAP positive cells in the synovium was identified by enzyme histochemistry. The level of the activity of TRAP and MMP-2 in the SF from the induced OA dogs was significantly higher than that of the control over a three-month period (P < 0.05). The TIMP-2 level in the SF was significantly lower in the induced OA dogs than in the control. However, there was no difference in TRAP activity in the serum. Histochemistry revealed a higher number of TRAP positive cells in the synovium from the induced OA dogs. Based on these data, we conclude that the activity of TRAP, MMP-2 and TIMP-2 in SF can be used as a biomarker to diagnose and monitor the early stages of OA.Keywords: tartrate-resistant acid phosphatase; matrix metalloproteinase-2; tissue inhibitor of matrix metalloproteinase-2; osteoarthritis; synovial fluid Supported by the Second Stage Brain Korea (BK) 21 Project and the Korea Science and Engineering Foundation

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“…Reliable biomarkers would not only reduce cost and time involved with diagnostics, but early detection of the disease would allow for the use of treatments that slow disease progression and extend life span (Mobasheri and Henrotin, 2011;Rorvik and Grondahl, 1995). The measurement of biomarkers using minimally invasive methods also allows sampling over time to monitor disease progression and adjust treatments accordingly (Hegemann et al, 2002;Lohmander, 1997). Although many candidate biomarkers have been suggested and studied, none have been validated to be pre-radiographic biomarkers specific to OA (Mobasheri and Henrotin, 2011).…”

Section: Biomarkersmentioning

confidence: 99%

Effects of dietary calcium fructoborate supplementation on joint comfort and flexibility and serum inflammatory markers in dogs with osteoarthritis

Price¹,

Godoy²,

Harper³

et al. 2017

Journal of Animal Science

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Symptoms of osteoarthritis (OA) afflict approximately 20% of adult dogs in NorthAmerica. Clinical signs consistent with OA include decreased range of motion of a joint, reduced physical activity, difficulty climbing stairs or onto furniture, and a reduced ability to rise from a lying position. A safe and effective nutraceutical supplement may benefit dogs suffering from OA. Calcium fructoborate (CFB), a mimetic of a naturally occurring molecule, has previously been reported to be safe and effective in humans with joint problems. The objective of this randomized, double-blinded, placebo-controlled study was to evaluate the short-term effects of CFB alone, or in combination with a blend of glucosamine hydrochloride (GH) and chondroitin sulfate (CS), on gait analysis, goniometry, serum inflammatory markers, and owner perception of pain in client-owned dogs. Sixty-four dogs with joint discomfort were recruited and 59 dogs (mean age = 8.42 ± 0.37 yr.; mean BW = 31.11 ± 1.28 kg) completed the study. All procedures were approved by the University of Illinois Institutional Animal Care and Use Committee, and pet owners signed an informed consent prior to study initiation. Dogs were randomly assigned to one of four treatments: placebo (60 mg fructose; n = 15), low dose (69 mg CFB; n = 14), high dose (127 mg CFB; n = 14), or combination (69 mg CFB, 500 mg GH and 200 mg CS; n = 16).Treatments were provided once daily as dietary supplements. Small dogs weighing up to 22.9 kg received 1 capsule/day, while large dogs weighing 23 to 50 kg received 2 capsules/day for 28 days. A physical examination, radiographs, goniometry measurements, gait analysis, blood sample collection, and the canine brief pain inventory (CBPI) questionnaire were performed and administered on days 0 and 28. As expected, a majority (69%) of the dogs were overweight or obese, with a body condition score (BCS) > 6 on a 9-point scale. Dogs fed the low dose (-2.93) and high dose (-2.21) of CFB were shown to improve (P < 0.05) in their ability to rise from a iii lying position from day 0 to day 28 compared to dogs fed the placebo (0.00), but no difference was observed for dogs fed the combination treatment. Dogs assigned the low dose of CFB also tended to have an improved pain severity score (PSS; -1.46; P = 0.08) and pain at its worst score (-2.14; P = 0.06) from day 0 to day 28 compared to dogs fed the placebo (0.05 and 0.00, respectively). Dogs fed the high dose of CFB had a greater increase (P = 0.05) in serum concentration of soluble receptor for advanced glycation end products (sRAGE) from day 0 to day 28 (7.88 ng/mL) compared to dogs fed the placebo (0.83 ng/mL). All blood metabolites were within reference range except total alkaline phosphatase and corticosteroid-induced alkaline phosphatase, which started and ended at concentrations greater than the upper reference range.Dogs assigned the high dose of CFB tended to have a greater reduction (P = 0.07) in serum chloride from day 0 to day 28 (-1.64 mmol/L) compared to dogs fed the low dose of ...

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Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders

Cited by 51 publications

References 34 publications

Tissue Inhibitor of Metalloproteinase 1 Activates Normal Human Granulocytes, Protects Them from Apoptosis, and Blocks Their Transmigration during Inflammation

Tissue Inhibitor of Metalloproteinase 1 Activates Normal Human Granulocytes, Protects Them from Apoptosis, and Blocks Their Transmigration during Inflammation

Tartrate-resistant acid phosphatase, matrix metalloproteinase-2 and tissue inhibitor metalloproteinase-2 in early stages of canine osteoarthritis

Effects of dietary calcium fructoborate supplementation on joint comfort and flexibility and serum inflammatory markers in dogs with osteoarthritis

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