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Correlation between μCT imaging, histology and functional capacity of the osteoarthritic knee in the rat model of osteoarthritis.

Bagi CM, Zakur DE, Berryman E, Andresen CJ, Wilkie D - J Transl Med (2015)

Bottom Line: The study results showed a negative impact of MMT surgery on the weight-bearing capacity of the operated limb.Bone analysis by μCT showed thickening of the subchondral bone beneath the damaged cartilage, loss of cancellous bone at the metaphysis and active osteophyte formation.The study emphasizes the need for using various methodologies that complement each other to provide a comprehensive understanding of the pathophysiology of OA at the organ, tissue and cellular levels.

View Article: PubMed Central - PubMed

Affiliation: Pfizer Global Research & Development, Global Science & Technology, 100 Eastern Point Road MS 8274-1359, Groton, CT, 06340, USA. cedo.bagi@pfizer.com.

ABSTRACT

Background: To acquire the most meaningful understanding of human arthritis, it is essential to select the disease model and methodology translatable to human conditions. The primary objective of this study was to evaluate a number of analytic techniques and biomarkers for their ability to accurately gauge bone and cartilage morphology and metabolism in the medial meniscal tear (MMT) model of osteoarthritis (OA).

Methods: MMT surgery was performed in rats to induce OA. A dynamic weight bearing system (DWB) system was deployed to evaluate the weight-bearing capacity of the front and hind legs in rats. At the end of a 10-week study cartilage pathology was evaluated by micro computed tomography (μCT), contrast enhanced μCT (EPIC μCT) imaging and traditional histology. Bone tissue was evaluated at the tibial metaphysis and epiphysis, including the subchondral bone. Histological techniques and dynamic histomorphometry were used to evaluate cartilage morphology and bone mineralization.

Results: The study results showed a negative impact of MMT surgery on the weight-bearing capacity of the operated limb. Surgery caused severe and extensive deterioration of the articular cartilage at the medial tibial plateau, as evidenced by elevated CTX-II in serum, EPIC μCT and histology. Bone analysis by μCT showed thickening of the subchondral bone beneath the damaged cartilage, loss of cancellous bone at the metaphysis and active osteophyte formation.

Conclusions: The study emphasizes the need for using various methodologies that complement each other to provide a comprehensive understanding of the pathophysiology of OA at the organ, tissue and cellular levels. Results from this study suggest that use of histology, μCT and EPIC μCT, and functional DWB tests provide powerful combination to fully assess the key aspects of OA and enhance data interpretation.

No MeSH data available.


Related in: MedlinePlus

% change in body weight placed on the front legs (a), on the rear right leg (c), and on the rear left leg (e) as well as the paw surface area of the front legs (b), on the rear right leg (d) and on the rear left leg (f) in sham and MMT rats. *p < 0.05 relative to sham rats for the same time point
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Fig1: % change in body weight placed on the front legs (a), on the rear right leg (c), and on the rear left leg (e) as well as the paw surface area of the front legs (b), on the rear right leg (d) and on the rear left leg (f) in sham and MMT rats. *p < 0.05 relative to sham rats for the same time point

Mentions: The MMT rats showed a different pattern of weight distribution compared to the sham rats. All the rats tended to shift weight bearing toward the front legs as they gained weight, but the MMT rats demonstrated this shift earlier; thus, at the 5-week time point, approximately 25 % of the body weight was already transferred to the front feet in MMT rats, compared to only 15 % in the sham rats. Additionally, the front paw-surface area was enlarged earlier in the MMT rats than in the sham rats. The total load placed on the hind legs was less in the MMT rats than in the sham controls, mainly because the rear right leg on which the MMT surgery was performed, exhibited less weight-bearing capacity and a smaller paw surface area than the right leg in the sham rats. Also, there is visible trend in MMT rats to increase the weight bearing of the left hind leg (Fig. 1).Fig. 1


Correlation between μCT imaging, histology and functional capacity of the osteoarthritic knee in the rat model of osteoarthritis.

Bagi CM, Zakur DE, Berryman E, Andresen CJ, Wilkie D - J Transl Med (2015)

% change in body weight placed on the front legs (a), on the rear right leg (c), and on the rear left leg (e) as well as the paw surface area of the front legs (b), on the rear right leg (d) and on the rear left leg (f) in sham and MMT rats. *p < 0.05 relative to sham rats for the same time point
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4549091&req=5

Fig1: % change in body weight placed on the front legs (a), on the rear right leg (c), and on the rear left leg (e) as well as the paw surface area of the front legs (b), on the rear right leg (d) and on the rear left leg (f) in sham and MMT rats. *p < 0.05 relative to sham rats for the same time point
Mentions: The MMT rats showed a different pattern of weight distribution compared to the sham rats. All the rats tended to shift weight bearing toward the front legs as they gained weight, but the MMT rats demonstrated this shift earlier; thus, at the 5-week time point, approximately 25 % of the body weight was already transferred to the front feet in MMT rats, compared to only 15 % in the sham rats. Additionally, the front paw-surface area was enlarged earlier in the MMT rats than in the sham rats. The total load placed on the hind legs was less in the MMT rats than in the sham controls, mainly because the rear right leg on which the MMT surgery was performed, exhibited less weight-bearing capacity and a smaller paw surface area than the right leg in the sham rats. Also, there is visible trend in MMT rats to increase the weight bearing of the left hind leg (Fig. 1).Fig. 1

Bottom Line: The study results showed a negative impact of MMT surgery on the weight-bearing capacity of the operated limb.Bone analysis by μCT showed thickening of the subchondral bone beneath the damaged cartilage, loss of cancellous bone at the metaphysis and active osteophyte formation.The study emphasizes the need for using various methodologies that complement each other to provide a comprehensive understanding of the pathophysiology of OA at the organ, tissue and cellular levels.

View Article: PubMed Central - PubMed

Affiliation: Pfizer Global Research & Development, Global Science & Technology, 100 Eastern Point Road MS 8274-1359, Groton, CT, 06340, USA. cedo.bagi@pfizer.com.

ABSTRACT

Background: To acquire the most meaningful understanding of human arthritis, it is essential to select the disease model and methodology translatable to human conditions. The primary objective of this study was to evaluate a number of analytic techniques and biomarkers for their ability to accurately gauge bone and cartilage morphology and metabolism in the medial meniscal tear (MMT) model of osteoarthritis (OA).

Methods: MMT surgery was performed in rats to induce OA. A dynamic weight bearing system (DWB) system was deployed to evaluate the weight-bearing capacity of the front and hind legs in rats. At the end of a 10-week study cartilage pathology was evaluated by micro computed tomography (μCT), contrast enhanced μCT (EPIC μCT) imaging and traditional histology. Bone tissue was evaluated at the tibial metaphysis and epiphysis, including the subchondral bone. Histological techniques and dynamic histomorphometry were used to evaluate cartilage morphology and bone mineralization.

Results: The study results showed a negative impact of MMT surgery on the weight-bearing capacity of the operated limb. Surgery caused severe and extensive deterioration of the articular cartilage at the medial tibial plateau, as evidenced by elevated CTX-II in serum, EPIC μCT and histology. Bone analysis by μCT showed thickening of the subchondral bone beneath the damaged cartilage, loss of cancellous bone at the metaphysis and active osteophyte formation.

Conclusions: The study emphasizes the need for using various methodologies that complement each other to provide a comprehensive understanding of the pathophysiology of OA at the organ, tissue and cellular levels. Results from this study suggest that use of histology, μCT and EPIC μCT, and functional DWB tests provide powerful combination to fully assess the key aspects of OA and enhance data interpretation.

No MeSH data available.


Related in: MedlinePlus