Characterization of experimentally induced post-traumatic osteoarthritis in the medial femorotibial joint of horses

Bolam, Courtney J.; Hurtig, Mark; Cruz, Antonio; McEwen, Beverly

doi:10.2460/ajvr.67.3.433

Cited by 46 publications

(76 citation statements)

References 68 publications

(91 reference statements)

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“…The authors acknowledge that a larger, longer experiment with more time points for analyses would be preferable, but careful interpretation of the results is possible. The model development phase of this experiment and others we have conducted 25,29 showed no animals will improve spontaneously, but the findings of the present study do not rule the possibly of relapse after treatment. The evidence of suppressed catabolic metabolism and lack of OA progression at early time points such as 90 and 147 days after injury should be considered preliminary, because osteoarthritis often presents an unrelenting challenge.…”

contrasting

confidence: 43%

“…[24][25][26][27][28] To ensure a defect was created that would not heal spontaneously in this species, 36 we created a challenging environment for articular repair by making two side-byside 6-mm diameter 30 MPa injuries. This impact force was within or above the range of deleterious impact forces reported for intact joints or osteochondral segments in other animal species such as the rabbit 37,38 and bovine, 24 and the resulting injury was larger than a similar model that used partial thickness defects in this species.…”

mentioning

confidence: 99%

“…[21][22][23] Models of knee OA after mechanical injury include contusive impact applied through an arthrotomy, 24 arthroscopically, 25 or to the closed joint 26 in the rabbit, 27 dog, 26,28 sheep, 29 and horse. 25 In the following studies the contusive impact model was used in the sheep knee (stifle) joint because of its similarity to the human knee, 30,31 the sheep's comparable body mass. Time points for analyses were chosen with two aims in mind: to demonstrate efficacy for BMP-7 treatment in posttraumatic osteoarthritis, and to explore the window of opportunity for successful therapy.…”

mentioning

confidence: 99%

“…Tissue blocks underwent routine paraffin embedding, and sections (5 mM) were stained with toluidine blue, hematoxylin and eosin, and safranin-O. Slides for TUNEL staining were prepared as per Bolam et al 25 using an ApopTag TM Plus peroxidase detection kit (#S7101 Chemicon International, Temecula, CA). Negative and positive controls for TUNEL staining were included in the kit but confirmatory studies in ovine cartilage were done using nuclease (SigmaAldrich, St. Louis, MO) pretreated normal cartilage and liver sections.…”

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confidence: 99%

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BMP‐7 protects against progression of cartilage degeneration after impact injury

Hurtig

Chubinskaya

Dickey

et al. 2008

Journal Orthopaedic Research

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In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 mg of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process. ß

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confidence: 99%

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BMP‐7 protects against progression of cartilage degeneration after impact injury

Hurtig

Chubinskaya

Dickey

et al. 2008

Journal Orthopaedic Research

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“…Joint disease is the most common cause of lameness in horses and represents a major caseload for the equine clinician (Bolam et al, 2006;Goodrich and Nixon, 2006). In mature horses, osteoarthritis is specifically important and results in considerable athletic and economic losses (Bolam et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of Mixed Extract of Panax Notoginseng, Rehmanniae Radix and Acanthopanacis Cortex (AIF) on Experimentally Induced Osteoarthritis

Park¹,

Kim²,

Ahn³

et al. 2010

Biomolecules and Therapeutics

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-The objective of the present study was to evaluate the effect of a mixed extract of three herbs, Panax Notoginseng, Rehmanniae Radix and Acanthopanacis cortex (AIF), for the treatment of horses with experimentally induced osteoarthritis. Twelve healthy male horses were included in this study. Horses were assigned to one of two groups: the AIF group (n=6) or the control group (n=6). Osteoarthritis was induced in all horses by intraarticular injection of sodium monoiodoacetate (0.12 mg/kg). Horses in the AIF group received 3 g of AIF with food daily, and those in the control group received food only. Treatment began on the day of intraarticular injection. Clinical and radiographic evaluations were performed every 2 weeks. At week 12, horses were euthanatized, and postmortem gross pathologic and histologic examinations of the middle carpal joint were performed. There were no significant differences in clinical values between the two groups. Radiographic evaluation revealed that the percentages of narrowness of joint space width in the control group were significantly higher than those in the AIF group (p＜0.02). On gross pathologic examination, the mean total dimensions of articular cartilage erosions and fibrillations in the control group (101.5 ± 41.5 mm 2 ) were significantly wider than those in the AIF group (29.3 ± 39.7 mm 2 ; p＜0.01). On histopathologic evaluation, significantly higher grades of staining intensity and lower empty lacunae (EL) ratios were found in the AIF group (p＜0.03). The present study revealed that AIF had significant disease modifying effects in horses with experimentally induced osteoarthritis.

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Surface topography as a tool to detect early changes in a posttraumatic equine model of osteoarthritis

Thampi

Tabbaa

Johnstone

et al. 2021

Journal Orthopaedic Research

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The equine model of posttraumatic osteoarthritis (OA) mimics certain aspects of the naturally occurring disease, both in horses and humans. The objective of this study was to assess articular cartilage degeneration in a posttraumatic OA model using the established macroscopic and microscopic scoring systems and compare them with a novel surface topography analysis. OA was induced in the carpal joint of 15 (n = 15) mixed breed horses. Surface changes on the articular cartilage were characterized using osteochondral blocks from the third carpal bone (C3) and radial carpal bone using surface topography, standard histological grading, and gross evaluation of the joints. Significant differences were observed between OA and non‐OA joints for gross evaluation scores. Microscopic scores of hematoxylin and eosin and Safranin O and Fast Green‐stained sections demonstrated no differences between OA and non‐OA joints. However, articular cartilage from the induced OA joint had significantly greater surface topography measurements compared with the sham treatment group, consistent with the changes seen on gross evaluation of joints. No significant correlations were noted between surface roughness measurements, histological assessment, and gross evaluation scores. The results suggest that surface topography analysis may provide a reliable objective approach to assess early changes in the cartilage surface in OA.

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Characterization of experimentally induced post-traumatic osteoarthritis in the medial femorotibial joint of horses

Abstract: Use of contusive impacts on the MFC of horses results in cartilage lesions that are similar to those described clinically, supporting trauma as a contributing factor in the natural pathogenesis of osteoarthritis.

Cited by 46 publications

References 68 publications

BMP‐7 protects against progression of cartilage degeneration after impact injury

BMP‐7 protects against progression of cartilage degeneration after impact injury

Effect of Mixed Extract of Panax Notoginseng, Rehmanniae Radix and Acanthopanacis Cortex (AIF) on Experimentally Induced Osteoarthritis

Surface topography as a tool to detect early changes in a posttraumatic equine model of osteoarthritis

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