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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

Two-dimensional µCT image of the proximal tibia from sham and MMT rat. Cortical and cancellous bone was measured for the entire epiphysis (E), whereas cancellous bone was evaluated at the metaphysis in the area of secondary spongiosa (M). Solid arrow indicates a lesser amount of cancellous bone in MMT rat; dotted arrow indicates thickening of the subchondral bone in MMT rat; arrowhead indicate osteophyte formation in MMT rat. Dotted blue square indicates area of epiphysis where UV micrographs are taken to show the new bone formation. Arrowheads indicate intensive bone remodeling of the osteophyte in MMT rat as judged by the presence of both calcein and alizarin red dye, whereas there is no osteophyte formation in the sham rat
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Fig2: Two-dimensional µCT image of the proximal tibia from sham and MMT rat. Cortical and cancellous bone was measured for the entire epiphysis (E), whereas cancellous bone was evaluated at the metaphysis in the area of secondary spongiosa (M). Solid arrow indicates a lesser amount of cancellous bone in MMT rat; dotted arrow indicates thickening of the subchondral bone in MMT rat; arrowhead indicate osteophyte formation in MMT rat. Dotted blue square indicates area of epiphysis where UV micrographs are taken to show the new bone formation. Arrowheads indicate intensive bone remodeling of the osteophyte in MMT rat as judged by the presence of both calcein and alizarin red dye, whereas there is no osteophyte formation in the sham rat

Mentions: The sham rats showed significantly higher BV (13 %), BV/TV ratio (18 %) bone surface (11 %), trabecular number (14 %) and connectivity diameter (21 %) and a lower trabecular separation index (24 %) compared to the MMT rats (Table 2; Fig. 2).Table 2


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)

Two-dimensional µCT image of the proximal tibia from sham and MMT rat. Cortical and cancellous bone was measured for the entire epiphysis (E), whereas cancellous bone was evaluated at the metaphysis in the area of secondary spongiosa (M). Solid arrow indicates a lesser amount of cancellous bone in MMT rat; dotted arrow indicates thickening of the subchondral bone in MMT rat; arrowhead indicate osteophyte formation in MMT rat. Dotted blue square indicates area of epiphysis where UV micrographs are taken to show the new bone formation. Arrowheads indicate intensive bone remodeling of the osteophyte in MMT rat as judged by the presence of both calcein and alizarin red dye, whereas there is no osteophyte formation in the sham rat
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Two-dimensional µCT image of the proximal tibia from sham and MMT rat. Cortical and cancellous bone was measured for the entire epiphysis (E), whereas cancellous bone was evaluated at the metaphysis in the area of secondary spongiosa (M). Solid arrow indicates a lesser amount of cancellous bone in MMT rat; dotted arrow indicates thickening of the subchondral bone in MMT rat; arrowhead indicate osteophyte formation in MMT rat. Dotted blue square indicates area of epiphysis where UV micrographs are taken to show the new bone formation. Arrowheads indicate intensive bone remodeling of the osteophyte in MMT rat as judged by the presence of both calcein and alizarin red dye, whereas there is no osteophyte formation in the sham rat
Mentions: The sham rats showed significantly higher BV (13 %), BV/TV ratio (18 %) bone surface (11 %), trabecular number (14 %) and connectivity diameter (21 %) and a lower trabecular separation index (24 %) compared to the MMT rats (Table 2; Fig. 2).Table 2

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