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Abstract

Case Description—A 16-year-old Thoroughbred gelding was examined because of chronic right forelimb lameness.

Clinical Findings—On radiographs of the right front foot, the distal interphalangeal (DIP) joint space was narrow, and osteophytes and periarticular bony proliferation indicative of severe osteoarthritis were seen. Arthrodesis of the right DIP joint was recommended to improve the horse's comfort on the limb.

Treatment and Outcome—The horse was anesthetized, and palmar and dorsal arthroscopic approaches were used to remove as much of the articular cartilage as was accessible. Holes were then drilled through the dorsal aspect of the hoof wall, and 3 transarticular, 5.5-mm cortical screws were placed in lag fashion through these holes across the distal phalanx and into the middle phalanx. Defects in the hoof wall were filled with gentamicin-impregnated polymethyl methacrylate plugs and sealed with cyanoacrylate. Eight months after surgery, fusion of the DIP joint was evident radiographically and the horse was sound at a walk.

Clinical Relevance—Transarticular placement of cortical screws through a dorsal hoof wall approach combined with arthroscopically guided cartilage removal can result in fusion of the DIP joint in horses.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the effects of interleukin- 1β (IL-1β) and tumor necrosis factor-α (TNF-α) on expression and regulation of several matrix-related genes by equine articular chondrocytes.

Sample Population—Articular cartilage harvested from grossly normal joints of 8 foals, 6 yearling horses, and 8 adult horses.

Procedure—Chondrocytes maintained in suspension cultures were treated with various doses of human recombinant IL-1β or TNF-α. Northern blots of total RNA from untreated and treated chondrocytes were probed with equine complementary DNA (cDNA) probes for cartilage matrix-related genes. Incorporation of 35S-sulfate, fluorography of 14C-proline labeled medium, zymography, and western blotting were used to confirm effects on protein synthesis.

Results—IL-1β and TNF-α increased steady-state amounts of mRNA of matrix metalloproteinases 1, 3, and 13 by up to 100-fold. Amount of mRNA of tissue inhibitor of metalloproteinase-1 also increased but to a lesser extent (1.5- to 2-fold). Amounts of mRNA of type-II collagen and link protein were consistently decreased in a dose-dependent manner. Amount of aggrecan mRNA was decreased slightly; amounts of biglycan and decorin mRNA were minimally affected.

Conclusions and Clinical Relevance—Treatment of cultured equine chondrocytes with IL-1β or TNF-α resulted in marked alterations in expression of various matrix and matrix-related genes consistent with the implicated involvement of these genes in arthritis. Expression of matrix metalloproteinases was increased far more than expression of their putative endogenous inhibitor. Results support the suggestion that IL-1β and TNF-α play a role in the degradation of articular cartilage in arthritis. (Am J Vet Res 2000;61: 624–630)

Full access
in American Journal of Veterinary Research

Abstract

Objective

To clone the entire coding sequence of equine matrix metalloproteinase-3 (MMP-3, stromelysin) and tissue inhibitor of metalloproteinase-1 (TIMP-1 ) and compare their nucleotide and amino acid sequences with those of MMP-3 and TIMP-1 from other species.

Samples

Articular cartilage harvested from the joints of 4 foals, 2 yearlings, and 3 adult horses.

Procedure

A cDNA library was constructed from mRNA extracted from equine chondrocytes. The library was screened and clones selected that contained the cDNA for MMP-3 and TIMP-1. The cDNA was sequenced and the nucleotide and deduced amino acid sequences compared with known sequences in other species. Northern blot analysis was performed, using the resulting cDNA clones.

Results

An 1803-bp cDNA for MMP-3 including the entire coding sequence of 1434 bases was cloned and sequenced. A 744-bp cDNA for TIMP-1 including the entire coding sequence of 624 bases was cloned and sequenced. Northern analysis revealed MMP-3 to hybridize to a single mRNA species at approximately 2.1 kb. TIMP-1 hybridized to a single mRNA species at approximately 0.8 kb.

Conclusions

MMP-3 and TIMP-1 were highly homologous to that of other species at the nucleotide and amino acid level although each had unique residues in part of the peptide that is generally conserved.

Clinical Relevance

Understanding the molecular structure of MMP-3 and TIMP-1 and the availability of their cDNA should allow a more detailed understanding of their balance in cartilage and the degradative processes in joint disease. (Am J Vet Res 1998; 59:1557-1562)

Free access
in American Journal of Veterinary Research

Objective

To determine type, distribution, and radiographic appearance of condylar fractures of the third metacarpal bone (MC-3) or third metatarsal bone (MT-3) in Thoroughbreds (TB), Standardbreds (SB), and Arabians, to assess long-term outcome of horses in which fractures were repaired surgically, and to identify variables associated with prognosis for return to racing.

Design

Retrospective study.

Animals

224 horses with 233 fractures.

Procedure

Medical records and radiographs obtained before and after treatment were reviewed. Racing performance before and after treatment was determined by reviewing race records.

Results

TB were overrepresented and SB were underrepresented, compared with the hospital population. Thoroughbreds had significantly more lateral condylar fractures and significantly more forelimb fractures than did SB. Thoroughbreds were less likely to race after treatment if they had complete, rather than incomplete, lateral condylar fracture or had concurrent proximal sesamoid bone fracture. Convalescent time for TB with medial condylar fractures of MT-3 was significantly longer than that for TB with lateral condylar fractures of MT-3.

Clinical Implications

Horses with condylar fractures of MC-3 and MT-3 that had minimal pathologic changes in the involved joint had a favorable prognosis for returning to racing after surgical treatment. Prognosis for horses with complete condylar fractures, particularly those with substantial pathologic changes in the involved joint, was worse. (J Am Vet Med Assoc 1998;212: 1757–1764)

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

Hexosamine concentration (an index of proteoglycan content), DNA content (an index of cellularity), and [35S]sulfate incorporation (an index of proteoglycan synthesis) of articular cartilage were measured in biopsy specimens from medial proximal sesamoid bone, medial condyle of the third metacarpal bone, and proximal dorsal rim of the proximal phalanx in both metacarpophalangeal joints of 6 adult horses. One limb was then placed in a fiberglass cast that extended down from the proximal portion of the metacarpus and enclosed the hoof; the other limb was not casted. After 30 days of stall confinement, additional specimens were taken from the medial proximal sesamoid bone, medial condyle of the third metacarpal bone, midproximal portion of the proximal phalanx, distal portion of the proximal phalanx, and proximal portion of the middle phalanx of both limbs for comparison.

Immobilization resulted in an apparent decrease in the hexosamine content of the cartilage when the 30-day immobilized vs 30-day mobilized specimens were analyzed. This decrease was accentuated by opposing trends in the 2 limbs. The immobilized cartilage tended to lose hexosamine, whereas the mobilized limb tended to gain hexosamine during the 30-day period; a similar trend also was seen with [35S] incorporation, but this trend was not statistically significant. The largest change was a significant increase in glycosaminoglycan synthesis in the mobilized limb, compared with little change in the immobilized joint cartilage.

We concluded that contralateral limbs are unsuitable for controls in immobilization studies because of their biological response to increased weight bearing. We also concluded that the changes in articular cartilage found following simple cast immoblization of 30 days' duration are minor and probably of little clinical consequence.

Free access
in American Journal of Veterinary Research

Summary

Bilateral, midshaft metacarpal osteotomies were performed in 11 sheep and bilateral, midshaft radial osteotomies were performed in 7 sheep. The lesions were repaired with bone plates. One of each pair of plates was luted with polymethylmethacrylate and all screws were tightened uniformly with a torque screwdriver. Sheep were allowed unrestricted exercise after surgery. At 8 weeks, 10 of 11 sheep with metacarpal osteotomies were sound and both osteotomies were healing. Seven were lame on the limb with the unluted plate during the first 3 weeks; 4 were never lame on either limb. The screws of the unluted plates were significantly (P < 0.01) looser at 8 weeks than those in the luted plates. All of the sheep with radial osteotomies were lame in the limb with the unluted plate. Four of 7 sheep had overt loosening of the unluted plates. One sheep only had mild screw loosening with continued alignment of the osteotomy. Two of 7 sheep fractured the radius with the luted plate; these 2 sheep were lame in the limb with the unluted plate and were using the limb with the luted plate vigorously. Excluding the 2 sheep with fractures, all had substantially more screw loosening in the unluted plate. Histologically, there were no discernible differences in the vascularity or porosity of the bone under the luted vs the unluted plates. The only adverse consequence of the luting technique was introduction of a small amount of polymethylmethacrylate into the osteotomy gap in 5 bones.

Free access
in American Journal of Veterinary Research

Summary

Hexosamine concentration, dna concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically.

Cellularity (measured as dna concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone.

Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.

Free access
in American Journal of Veterinary Research

SUMMARY

Using arthroscopic technique, identical diameter defects were created in the proximal articular surface of both intermediate carpal bones of 6 horses. One of each pair of defects was deepened to penetrate the subchondral plate. Removed cartilage was assayed for [35S] sulfate incorporation, total hexosamine content, and dna content. Six weeks later, cartilage was harvested and similarly analyzed from the distolateral portion of the radius directly opposite the created lesions and the distomedial portion of the radius distant from the lesion. The repair tissue filling the full-thickness defect and the cartilage at the periphery of the partial-thickness lesion also were analyzed.

There was a marked increase in synthetic activity (35S sulfate incorporation) opposite the full-thickness defect, compared with the cartilage opposite the partial-thickness defect. A marked decrease in glycosaminoglycan content in the cartilage opposite the full-thickness defect was found as compared with that opposite the partialthickness defect. The repair tissue filling the full-thickness defect was highly cellular, high in synthetic activity, but low in glycosaminoglycan content. Insignificant changes occurred in the cartilage adjacent to the partialthickness defect. On the basis of these results, we suggest that full-thickness defects at 6 weeks result in more detrimental change to the cartilage opposite it than do partial-thickness lesions of the same diameter.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of interleukin (IL)-1β and glucocorticoids on total glycosaminoglycan (GAG) loss and aggrecanase-mediated matrix degradation in equine cartilage.

Sample Population—Cartilage from 24 equine cadavers free of sepsis and musculoskeletal disease.

Procedures—Effects of IL-1β, IL-1β with glucocorticoids (dexamethasone and triamcinolone, 10−6 and 10−7M), and glucocorticoids alone on degradation of equine articular and nasal cartilage explants were assessed by measuring GAG release in media and GAG content in cartilage. Aggrecanase-mediated cleavage within the interglobular domain at Glu373-Ala374 was evaluated via western blot analysis and ELISAs. Steady-state mRNA concentrations of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, and ADAMTS5 were assessed by use of real-time reverse transcriptase PCR assay (cartilage explants) and northern blot analysis (cell culture).

Results—IL-1β increased GAG release and aggrecanase activity (11-fold). The MMP-3, MMP-13, and ADAMTS4 mRNA were upregulated with IL-1β, whereas ADAMTS5 mRNA was increased (13-fold), but significantly less than ADAMTS4 mRNA (27-fold), suggesting a role for both ADAMTS4 and ADAMTS5 in degradation of cytokine-stimulated cartilage. Despite downregulation of MMP-3 and MMP-13 mRNA, glucocorticoids did not alter GAG degradation. A further increase in aggrecanase activity was detected with ELISAs and western blot analysis, whereas ADAMTS4 mRNA was downregulated and ADAMTS5 mRNA was maintained or upregulated.

Conclusions and Clinical Relevance—MMP-3, MMP-13, and ADAMTS4 were regulated differently than ADAMTS5. Glucocorticoids increased aggrecanase activity despite down-regulation of ADAMTS4 mRNA, suggesting a major role of ADAMTS5. Effects of glucocorticoids on aggrecanase activity have important implications in terms of treatment.

Full access
in American Journal of Veterinary Research

Summary:

Medical records of 57 horses admitted between 1980 and 1991 because of basal sesamoidean fractures were evaluated. Radiographic measurements of fragment size and fracture characteristics were recorded to determine their relationship to outcome. A successful outcome was assessed on the basis of the ability to return to racing, ability to race more than one time, and ability to finish first, second, or third. Any change in racing class also was assessed.

There was a significant (P < 0.001) overrepresentation of Thoroughbreds, compared with other breeds in the hospital population. Fractures of the forelimbs accounted for 50 of the 57 fractures, and the right front medial sesamoid was affected significantly (P < 0.0001) more frequently than other proximal sesamoids.

Fifty-nine percent of the horses returned to race at least 1 time regardless of treatment, and 41% finished first, second, or third. Horses with smaller fragments (shorter dorsopalmar length) tended to do better than horses with larger fragments. Horses without comminuted fractures tended to do better than horses with comminuted fractures, and horses with fragments only mildly (< 3 mm) displaced had significantly (P < 0.05) better outcomes than did horses with severe displacement of fragments. Only 19% of the horses with moderate (> 3 mm) displacement of fragments raced more than once, whereas 63% of horses with mild displacement of fragments returned to race more than once.

Seventy-three percent of the horses that had the fragment removed surgically returned to race, and 57% dropped in class. Only 48% of the horses that did not have the fragment removed returned to race, and 87% dropped in class. Mean time for return to racing was 8.6 months for horses that had the fragment removed, and 6.5 months for those that did not.

Free access
in Journal of the American Veterinary Medical Association