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Eugene J M A Thonar - One of the best experts on this subject based on the ideXlab platform.

  • matrix replenishment by intervertebral disc cells after chemonucleolysis in vitro with chondroitinase abc and Chymopapain
    The Spine Journal, 2007
    Co-Authors: Kazuhiro Chiba, Koichi Masuda, Gunnar B J Andersson, Shigeki Momohara, Eugene J M A Thonar
    Abstract:

    Abstract Background context One of the advantages of chemonucleolysis for the treatment of a herniated intervertebral disc is the potential for the disc to self-repair. It has been suggested that the enzymes used for chemonucleolysis differentially affect the potential of the disc cells to promote repair. Purpose To test the ability of nucleus pulposus and anulus fibrosus cells to repair the extracellular matrix degraded in vitro by either chondroitinase ABC or Chymopapain. Study design An alginate cell culture system was used to monitor the progress of matrix repair after chemonucleolysis in vitro. Methods Rabbit nucleus pulposus or anulus fibrosus cells precultured for 10 days in alginate gel were briefly exposed to low concentrations of chondroitinase ABC or Chymopapain and then returned to normal culture conditions for up to 4 weeks. At each time point, the contents of DNA and matrix macromolecules and proteoglycan synthesis were measured. Results The DNA content of enzyme-treated alginate beads during the following 4 weeks of culture was higher in the chondroitinase ABC group than in the Chymopapain group (NP, p Conclusions Intervertebral disc cells exposed to chondroitinase ABC reestablish a matrix richer in proteoglycan than cells exposed to Chymopapain. This may be because of differences in the substrate spectrum of each enzyme. Although these results cannot be translated directly to the in vivo situation, they suggest the possibility that cells in discs subjected to chondroitinase ABC–induced chemonucleolysis retain a greater ability to replenish their extracellular matrix with proteoglycans than cells in discs exposed to Chymopapain.

  • the use of intra articular na hyaluronate as a potential chondroprotective device in experimentally induced acute articular cartilage injury and repair in rabbits
    Journal of Orthopaedic Research, 2003
    Co-Authors: James M. Williams, Vineeta Rayan, Rick D Sumner, Eugene J M A Thonar
    Abstract:

    Abstract Objective: This study examined if viscosupplementation from intra-articular administration of a commercially available form of hyaluronan (HA) could promote the restoration of proteoglycan (PG) depletion induced by Chymopapain and then if the repair could be maintained once HA treatment was discontinued. Methods: Animals received cartilage injury with intra-articular Chymopapain (2.0 mg) followed by weekly treatment with intra-articular HA. HA treated animals were compared to injured animals with no treatment, contralateral untreated joints and joints from normal controls. The effect of intra-articular HA alone on articular cartilage was also examined. Results: Serum keratan sulfate levels confirmed degradation of the cartilage PGs in the Chymopapain-injected knees. Intra-articular Chymopapain resulted in marked loss of PGs. There were no significant differences among the control groups (untreated control, HA/800 treatment only). HA treatment did not affect the loss of PGs caused by Chymopapain after 42 days. However, in animals receiving Chymopapain injury followed by weekly HA treatment for 42 days and then 42 days of free cage activity without HA, cartilage PG contents were significantly increased. Intra-articular HA alone had no effect on the articular cartilage. Conclusion: The results in the present study suggest a potential protective effect of HA on Chymopapain-induced acute articular cartilage injury in rabbits that, in time, permits damaged cartilage to resynthesize matrix PGs after the HA treatment is discontinued.

  • The effect of bone remodeling inhibition by zoledronic acid in an animal model of cartilage matrix damage.
    Osteoarthritis and cartilage, 2002
    Co-Authors: Carol Muehleman, Eugene J M A Thonar, J. Green, James M. Williams, Klaus E. Kuettner, Dale R. Sumner
    Abstract:

    Abstract Objective The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of cartilage matrix damage. Design New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint with the cartilage matrix degradation enzyme, Chymopapain; (3) injected into one knee joint with Chymopapain and also given subcutaneous injections of the bisphosphonate, zoledronic acid, three times per week until sacrifice at either day 28 or 56 post-Chymopapain-injection; (4) received only the zoledronic acid injections. At sacrifice, the knee joints were examined grossly and histologically, and biochemically for proteoglycan content. Urine samples were analysed, at intervals, for levels of collagen cross-links which are biochemical markers of cartilage and bone. Results Animals receiving both intraarticular Chymopapain injections and subcutaneous zoledronic acid injections displayed a significantly lower degree of grossly and histologically detectable cartilage degeneration on the tibial articular surfaces (the articular surface displaying the greatest degree of degeneration) than did animals only receiving the Chymopapain injections. In addition, urinary levels of collagen cross-links for bone and cartilage were significantly higher in those animals only receiving Chymopapain injections. Conclusion The bone resorption observed after Chymopapain injection into the rabbit knee joint can be inhibited through the use of the bisphosphonate, zoledronic acid. Furthermore, zoledronic acid does not increase the level of cartilage degeneration and appears to provide some level of chondroprotection in this model.

  • the dose related effect of intradiscal Chymopapain on rabbit intervertebral discs
    Spine, 1994
    Co-Authors: Douglass P Kiester, Eugene J M A Thonar, James M. Williams, Gunnar Andersson, Thomas W Mcneill
    Abstract:

    Study design This study analyzed the histological and biochemical responses of intervertebral disc tissue to intradiscal injection of varying amounts of Chymopapain. Objective To determine the appropriate amount of Chymopapain needed to accomplish effective degradation of proteoglycans (PG) in the nucleus pulposus of intervertebral discs. Summary of background data Chymopapain is an accepted treatment alternative for patients with disc herniations. The recommended clinical dose of 2,000-4,000 pKats per injection is derived from early animal studies and empirical results in man. A lower effective dose could reduce the complication rate while providing similar clinical results. Methods Twenty to 4,000 pKat of Chymopapain was injected into rabbit discs, and the level of keratan sulfate (KS) epitope in serum was measured at different times after the injection. The animals were killed after 6 days and the injected and two neighboring discs were examined histologically. Results The serum KS level did not change appreciably after injection of 20 pKat, rose moderately at 100 and 200 pKat, and rose strongly at 500 pKat. Doses greater than 500 pKat did not result in further increase in the KS level. Conclusion Degradation of the disc proteoglycans is dose dependent and reaches a maximum at 500 pKat. Higher doses appear not to cause further loss of aggrecan molecules, and injection of more than 1,000 pKat produces significant annular destruction.

  • elevation in urinary levels of pyridinium cross links of collagen following Chymopapain induced degradation of articular cartilage in the rabbit knee provides evidence of metabolic changes in bone
    Osteoarthritis and Cartilage, 1993
    Co-Authors: Daniel Uebelhart, Eugene J M A Thonar, Daniel Pietryla, James M. Williams
    Abstract:

    To measure urinary levels of two pyridinium cross-links of collagens at various times, rabbits were injected in the left knee with 0.2 mg (N = 11) or 2.0 mg Chymopapain (N = 11). Urinary levels of the bone-specific deoxy-pyridinoline cross-link and of the hydroxylysyl pyridinoline cross-link, found in large amounts in articular cartilage and bone, were measured by high performance liquid chromatography (HPLC). The urinary levels were correlated with histological evidence of progressive articular cartilage destruction in animals injected with 2.0 mg Chymopapain and of successful repair in rabbits injected with the lower dose. Rabbits injected with 2.0 mg Chymopapain showed a very large increase in urinary levels of deoxy-pyridinoline during the first 30 days after the injection. This rise was not seen in animals injected with the lower dose. A rise in urinary level of the hydroxylysyl pyridonline cross-link was observed in all rabbits but was more pronounced and lasted longer in animals receiving the higher dose. The failure of rabbits injected with 2.0 mg Chymopapain to repair the damaged articular cartilage was strongly associated with a marked increase in the catabolism of the bone-specific deoxy-pyridinoline cross-link and to a lesser extent with the catabolism of the hydroxylysyl pyridinoline found in bone and in articular cartilage.

Atiyatul Qadeer - One of the best experts on this subject based on the ideXlab platform.

  • 1-Anilino-8-Naphthalene Sulfonate (ANS) Is Not a Desirable Probe for Determining the Molten Globule State of Chymopapain
    2015
    Co-Authors: Atiyatul Qadeer, Gulam Rabbani, Nida Zaidi, Ejaz Ahmad, Javed M. Khan, Rizwan H. Khan
    Abstract:

    The molten globule (MG) state of proteins is widely detected through binding with 1-anilino-8-naphthalene sulphonate (ANS), a fluorescent dye. This strategy is based upon the assumption that when in molten globule state, the exposed hydrophobic clusters of protein are readily bound by the nonpolar anilino-naphthalene moiety of ANS molecules which then produce brilliant fluorescence. In this work, we explored the acid-induced unfolding pathway of Chymopapain, a cysteine proteases from Carica papaya, by monitoring the conformational changes over a pH range 1.0–7.4 by circular dichroism, intrinsic fluorescence, ANS binding, acrylamide quenching, isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). The spectroscopic measurements showed that although maximum ANS fluorescence intensity was observed at pH 1.0, however protein exhibited,80 % loss of secondary structure which does not comply with the characteristics of a typical MG-state. In contrast at pH 1.5, Chymopapain retains substantial amount of secondary structure, disrupted side chain interactions, increased hydrodynamic radii and nearly 30-fold increase in ANS fluorescence with respect to the native state, indicating that MG-state exists at pH 1.5 and not at pH 1.0. ITC measurements revealed that ANS molecules bound to Chymopapain via hydrophobic interaction were more at pH 1.5 than at pH 1.0. However, a large number of ANS molecules were also involved in electrostatic interaction with protein at pH 1.0 which, together with hydrophobically interacted molecules, may be responsible for maximum ANS fluorescence. We conclude that maximu

  • Effect of pH on ANS binding of Chymopapain.
    2013
    Co-Authors: Atiyatul Qadeer, Gulam Rabbani, Nida Zaidi, Ejaz Ahmad, Javed M. Khan, Rizwan H. Khan
    Abstract:

    (A) ANS fluorescence spectra of Chymopapain at pH 7.4 (-▪-), pH 3.0 (-○-), pH 1.5 (-▴-), pH 1.0 (-•-) and in the presence of 6M GuHCl (-□-). (B) Changes in ANS fluorescence intensity of Chymopapain as a function of pH at 480 nm. Inset: pH dependence of ANS emission maxima (λmax) of Chymopapain. Protein concentration was 8 µM. The molar ratio of protein to ANS was 1∶50.

  • Effect of pH on far-UV CD of Chymopapain.
    2013
    Co-Authors: Atiyatul Qadeer, Gulam Rabbani, Nida Zaidi, Ejaz Ahmad, Javed M. Khan, Rizwan H. Khan
    Abstract:

    (A) Far-UV CD spectra of Chymopapain at pH 7.4 (-▪-), pH 1.5 (-▴-), pH 1.0 (-•-) and in the presence of 6M GuHCl (-□-). (B) pH dependent changes in mean residual ellipticity (MRE) at 222 nm of Chymopapain. Protein concentration was 8 µM.

  • Effect of pH on near-UV CD of Chymopapain.
    2013
    Co-Authors: Atiyatul Qadeer, Gulam Rabbani, Nida Zaidi, Ejaz Ahmad, Javed M. Khan, Rizwan H. Khan
    Abstract:

    (A) Near-UV CD spectra of Chymopapain at pH 7.4 (-▪-), pH 3.0 (-○-), pH 1.5 (-▴-), pH 1.0 (-•-) and in the presence of 6M GuHCl (-□-). (B) pH dependent alterations in mean residual ellipticity (MRE) at 272 nm of Chymopapain. Protein concentration was 40 µM.

  • pH dependence of Trp fluorescence of Chymopapain.
    2013
    Co-Authors: Atiyatul Qadeer, Gulam Rabbani, Nida Zaidi, Ejaz Ahmad, Javed M. Khan, Rizwan H. Khan
    Abstract:

    (A) Fluorescence emission spectra of Chymopapain at pH 7.4 (-▪-), pH 3.0 (-○-), pH 1.5 (-▴-), pH 1.0 (-•-) and in the presence of 6M GuHCl (-□-). (B) Changes in relative fluorescence intensity (RFI) at 345 nm (-□-) and emission maxima (-▪-) of Chymopapain as a function of pH. Spectra were obtained by exciting Trp at 295 nm. Protein concentration was 8 µM.

Rizwan Hasan Khan - One of the best experts on this subject based on the ideXlab platform.

  • 1 anilino 8 naphthalene sulfonate ans is not a desirable probe for determining the molten globule state of Chymopapain
    PLOS ONE, 2012
    Co-Authors: Atiyatul Qadeer, Gulam Rabbani, Nida Zaidi, Ejaz Ahmad, Javed Masood Khan, Rizwan Hasan Khan
    Abstract:

    The molten globule (MG) state of proteins is widely detected through binding with 1-anilino-8-naphthalene sulphonate (ANS), a fluorescent dye. This strategy is based upon the assumption that when in molten globule state, the exposed hydrophobic clusters of protein are readily bound by the nonpolar anilino-naphthalene moiety of ANS molecules which then produce brilliant fluorescence. In this work, we explored the acid-induced unfolding pathway of Chymopapain, a cysteine proteases from Carica papaya, by monitoring the conformational changes over a pH range 1.0–7.4 by circular dichroism, intrinsic fluorescence, ANS binding, acrylamide quenching, isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). The spectroscopic measurements showed that although maximum ANS fluorescence intensity was observed at pH 1.0, however protein exhibited ∼80% loss of secondary structure which does not comply with the characteristics of a typical MG-state. In contrast at pH 1.5, Chymopapain retains substantial amount of secondary structure, disrupted side chain interactions, increased hydrodynamic radii and nearly 30-fold increase in ANS fluorescence with respect to the native state, indicating that MG-state exists at pH 1.5 and not at pH 1.0. ITC measurements revealed that ANS molecules bound to Chymopapain via hydrophobic interaction were more at pH 1.5 than at pH 1.0. However, a large number of ANS molecules were also involved in electrostatic interaction with protein at pH 1.0 which, together with hydrophobically interacted molecules, may be responsible for maximum ANS fluorescence. We conclude that maximum ANS-fluorescence alone may not be the criteria for determining the MG of Chymopapain. Hence a comprehensive structural analysis of the intermediate is essentially required.

Keith Brocklehurst - One of the best experts on this subject based on the ideXlab platform.

  • the structural origins of the unusual specificities observed in the isolation of Chymopapain m and actinidin by covalent chromatography and the lack of inhibition of Chymopapain m by cystatin
    Biochemical Journal, 1995
    Co-Authors: Mark P Thomas, Chandra S Verma, S M Boyd, Keith Brocklehurst
    Abstract:

    Abstract 1. The selectivity observed when the potentially general technique for the isolation of fully active forms of cysteine proteinases, covalent chromatography by thiol-disulphide interchange, is applied to Chymopapain M and to actinidin was investigated by a combination of experimentation and computer modelling. Neither of these enzymes is able to react with the original Sepharose-GSH-2-dipyridyl disulphide gel, but fully active forms of both enzymes are obtained by using Sepharose-2-hydroxypropyl-2'-dipyridyl disulphide gel, which is both electrically neutral and sterically less demanding than the GSH gel. Electrostatic potential calculations, minimization and molecular-dynamics simulations provide explanations for the unusual, but different, specificities exhibited by actinidin and Chymopapain M in the interactions of their active centres with ligands. 2. The unique behaviour of Chymopapain M in exerting an almost absolute specificity for substrates with glycine at the P1 position and in resisting inhibition by cystatin was examined by the computer-modelling techniques. A new, modelled, structure of the complete chicken egg-white cystatin molecule based on the crystal structure of a short form of cystatin was deduced as a necessary prerequisite. The results suggest that electrostatic repulsion prevents reaction of actinidin with the GSH gel, whereas a steric 'cap' resulting from a unique arginine-65-glutamic acid-23 interaction in Chymopapain M prevents reaction of the gel with this enzyme and accounts for the lack of its inhibition by cystatin and its specificity in catalysis. 3. Use of Chymopapain M as a structural variant of papain demonstrates the validity of the predictions of Lowe and Yuthavong [Biochem. J. (1971) 124, 107-115] relating to the structural requirements and binding characteristics of the S1 subsite of papain.

  • structure of Chymopapain m the late eluted Chymopapain deduced by comparative modelling techniques and active centre characteristics determined by ph dependent kinetics of catalysis and reactions with time dependent inhibitors the cys 25 his 159 ion pair is insufficient for catalytic competence in both Chymopapain m and papain
    Biochemical Journal, 1994
    Co-Authors: Mark P Thomas, Christopher M Topham, D Kowlessur, G W Mellor, Emrys W Thomas, David Whitford, Keith Brocklehurst
    Abstract:

    Chymopapain M, the monothiol cysteine proteinase component of the Chymopapain band eluted after Chymopapains A and B in cation-exchange chromatography, was isolated from the dried latex of Carica papaya and characterized by kinetic and chromatographic analysis. This late-eluted Chymopapain is probably a component of the cysteine proteinase fraction of papaya latex discovered by Schack [(1967) Compt. Rend. Trav. Lab. Carlsberg 36, 67-83], named papaya peptidase B by Lynn [(1979) Biochim. Biophys. Acta 569, 193-201] and partially characterized by Polgar [(1981) Biochim. Biophys. Acta 658, 262-269] and is the enzyme with unusual specificity characteristics (papaya proteinase IV) that Buttle, Kembhavi, Sharp, Shute, Rich and Barrett [Biochem. J. (1989) 261, 469-476] claimed to be a previously undetected cysteine proteinase eluted from a cation-exchange column near to the early-eluted Chymopapains. A study of the time-dependent chromatographic consequences of thiol-dependent proteolysis of the components of papaya latex is reported. Chymopapain M was isolated by (i) affinity chromatography followed by separation from papain using cation-exchange f.p.l.c. on a Mono S HR5/5 column and (ii) cation-exchange chromatography followed by an unusual variant of covalent chromatography by thiol-disulphide interchange. The existence in Chymopapain M of a nucleophilic interactive Cys/His catalytic-site system analogous to those in papain (EC 3.4.22.2) and other cysteine proteinases was deduced from the characteristics shape of the pH-second-order rate constant (k) profiles for its reactions with 2,2'-dipyridyl disulphide and ethyl 2-pyridyl disulphide. Analysis of the pH-k data for the reactions of Chymopapain M with the 2-pyridyl disulphides and with 4,4'-dipyridyl disulphide permits the assignment of molecular pKa values of 3.4 and 8.7 to the formation and subsequent dehydronation of the Cys-S-/His-Im+H state of the catalytic site and reveals three other kinetically influential ionizations with pKa values 3.4, 4.3 and 5.6. The pH-dependences of kcat./Km for the hydrolysis of N-acetyl-L-Phe-Gly-4-nitroanilide at 25.0 degrees C and I0.1 M catalysed by Chymopapain M and papain were determined. For both enzymes, little catalytic activity (5-7% of the maximal) develops consequent on formation of the catalytic site Cys-S-/His-Im+H ion-pair state (across pKa 3.4 for both enzymes). For papain, full expression of Kcat./Km for the uncharged substrate requires only the additional hydronic dissociation with pKa 4.2. By contrast, full expression of kcat./Km for Chymopapain M requires additional hydronic dissociation with pKa values of 4.3 and 5.6.(ABSTRACT TRUNCATED AT 400 WORDS)

James M. Williams - One of the best experts on this subject based on the ideXlab platform.

  • the use of intra articular na hyaluronate as a potential chondroprotective device in experimentally induced acute articular cartilage injury and repair in rabbits
    Journal of Orthopaedic Research, 2003
    Co-Authors: James M. Williams, Vineeta Rayan, Rick D Sumner, Eugene J M A Thonar
    Abstract:

    Abstract Objective: This study examined if viscosupplementation from intra-articular administration of a commercially available form of hyaluronan (HA) could promote the restoration of proteoglycan (PG) depletion induced by Chymopapain and then if the repair could be maintained once HA treatment was discontinued. Methods: Animals received cartilage injury with intra-articular Chymopapain (2.0 mg) followed by weekly treatment with intra-articular HA. HA treated animals were compared to injured animals with no treatment, contralateral untreated joints and joints from normal controls. The effect of intra-articular HA alone on articular cartilage was also examined. Results: Serum keratan sulfate levels confirmed degradation of the cartilage PGs in the Chymopapain-injected knees. Intra-articular Chymopapain resulted in marked loss of PGs. There were no significant differences among the control groups (untreated control, HA/800 treatment only). HA treatment did not affect the loss of PGs caused by Chymopapain after 42 days. However, in animals receiving Chymopapain injury followed by weekly HA treatment for 42 days and then 42 days of free cage activity without HA, cartilage PG contents were significantly increased. Intra-articular HA alone had no effect on the articular cartilage. Conclusion: The results in the present study suggest a potential protective effect of HA on Chymopapain-induced acute articular cartilage injury in rabbits that, in time, permits damaged cartilage to resynthesize matrix PGs after the HA treatment is discontinued.

  • The effect of bone remodeling inhibition by zoledronic acid in an animal model of cartilage matrix damage.
    Osteoarthritis and cartilage, 2002
    Co-Authors: Carol Muehleman, Eugene J M A Thonar, J. Green, James M. Williams, Klaus E. Kuettner, Dale R. Sumner
    Abstract:

    Abstract Objective The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of cartilage matrix damage. Design New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint with the cartilage matrix degradation enzyme, Chymopapain; (3) injected into one knee joint with Chymopapain and also given subcutaneous injections of the bisphosphonate, zoledronic acid, three times per week until sacrifice at either day 28 or 56 post-Chymopapain-injection; (4) received only the zoledronic acid injections. At sacrifice, the knee joints were examined grossly and histologically, and biochemically for proteoglycan content. Urine samples were analysed, at intervals, for levels of collagen cross-links which are biochemical markers of cartilage and bone. Results Animals receiving both intraarticular Chymopapain injections and subcutaneous zoledronic acid injections displayed a significantly lower degree of grossly and histologically detectable cartilage degeneration on the tibial articular surfaces (the articular surface displaying the greatest degree of degeneration) than did animals only receiving the Chymopapain injections. In addition, urinary levels of collagen cross-links for bone and cartilage were significantly higher in those animals only receiving Chymopapain injections. Conclusion The bone resorption observed after Chymopapain injection into the rabbit knee joint can be inhibited through the use of the bisphosphonate, zoledronic acid. Furthermore, zoledronic acid does not increase the level of cartilage degeneration and appears to provide some level of chondroprotection in this model.

  • the dose related effect of intradiscal Chymopapain on rabbit intervertebral discs
    Spine, 1994
    Co-Authors: Douglass P Kiester, Eugene J M A Thonar, James M. Williams, Gunnar Andersson, Thomas W Mcneill
    Abstract:

    Study design This study analyzed the histological and biochemical responses of intervertebral disc tissue to intradiscal injection of varying amounts of Chymopapain. Objective To determine the appropriate amount of Chymopapain needed to accomplish effective degradation of proteoglycans (PG) in the nucleus pulposus of intervertebral discs. Summary of background data Chymopapain is an accepted treatment alternative for patients with disc herniations. The recommended clinical dose of 2,000-4,000 pKats per injection is derived from early animal studies and empirical results in man. A lower effective dose could reduce the complication rate while providing similar clinical results. Methods Twenty to 4,000 pKat of Chymopapain was injected into rabbit discs, and the level of keratan sulfate (KS) epitope in serum was measured at different times after the injection. The animals were killed after 6 days and the injected and two neighboring discs were examined histologically. Results The serum KS level did not change appreciably after injection of 20 pKat, rose moderately at 100 and 200 pKat, and rose strongly at 500 pKat. Doses greater than 500 pKat did not result in further increase in the KS level. Conclusion Degradation of the disc proteoglycans is dose dependent and reaches a maximum at 500 pKat. Higher doses appear not to cause further loss of aggrecan molecules, and injection of more than 1,000 pKat produces significant annular destruction.

  • elevation in urinary levels of pyridinium cross links of collagen following Chymopapain induced degradation of articular cartilage in the rabbit knee provides evidence of metabolic changes in bone
    Osteoarthritis and Cartilage, 1993
    Co-Authors: Daniel Uebelhart, Eugene J M A Thonar, Daniel Pietryla, James M. Williams
    Abstract:

    To measure urinary levels of two pyridinium cross-links of collagens at various times, rabbits were injected in the left knee with 0.2 mg (N = 11) or 2.0 mg Chymopapain (N = 11). Urinary levels of the bone-specific deoxy-pyridinoline cross-link and of the hydroxylysyl pyridinoline cross-link, found in large amounts in articular cartilage and bone, were measured by high performance liquid chromatography (HPLC). The urinary levels were correlated with histological evidence of progressive articular cartilage destruction in animals injected with 2.0 mg Chymopapain and of successful repair in rabbits injected with the lower dose. Rabbits injected with 2.0 mg Chymopapain showed a very large increase in urinary levels of deoxy-pyridinoline during the first 30 days after the injection. This rise was not seen in animals injected with the lower dose. A rise in urinary level of the hydroxylysyl pyridonline cross-link was observed in all rabbits but was more pronounced and lasted longer in animals receiving the higher dose. The failure of rabbits injected with 2.0 mg Chymopapain to repair the damaged articular cartilage was strongly associated with a marked increase in the catabolism of the bone-specific deoxy-pyridinoline cross-link and to a lesser extent with the catabolism of the hydroxylysyl pyridinoline found in bone and in articular cartilage.