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Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis.

Naraoka T, Ishibashi Y, Tsuda E, Yamamoto Y, Kusumi T, Toh S - Arthritis Res. Ther. (2013)

Bottom Line: A Tukey's honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results.Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control.This effect appears to be exerted by promotion of type II collagen synthesis predominantly.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Collagen peptides have been reported to possess various biological activities for various cell types. The purposes of this study were, first, to examine the therapeutic effects of collagen tripeptide (Ctp) in rabbit osteoarthritis and, second, to explore a synergetic effect with hyaluronan (HA).

Methods: Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in 72 Japanese white rabbits and they were divided into four groups (control, Ctp, HA and Ctp/HA). Each material was injected weekly into the knee, and knee joint samples were collected 5, 10 and 15 weeks after surgery. Macroscopic and histomorphological analyses of cartilage were conducted. Expression of type II collagen and matrix metalloproteinase-13 was also analyzed immunohistochemically. A Tukey's honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results.

Results: All treatment groups exhibited slightly higher resistance to the progression of osteoarthritis than the control group macroscopically 15 weeks after surgery. Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control. Immunohistochemically, both Ctp-treated and Ctp/HA-treated groups had significantly increased type II collagen-positive chondrocytes at the fifth week after the surgery, although the numbers of matrix metalloproteinase-13-positive chondrocytes were not affected.

Conclusion: Periodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by anterior cruciate ligament transection in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly.

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Inhibitory effects of collagen tripeptide, hyaluronan and collagen tripeptide/hyaluronan on osteoarthritis development. (A) Histologies of the medial femoral condylar cartilage stained with safranin-O. Arrow indicates cluster formation (original magnification ×100). (B) Appearance of safranin-O (×100) staining in the medial femoral condylar cartilage from a normal rabbit knee. (C) Osteoarthritis Research Society International (OARSI) {AU Query: Confirm definition} score for medial femoral condylar cartilage lesions in each group 5, 10 and 15 weeks after surgery. Ctp, collagen tripeptide; HA, hyaluronan. Data presented as mean ± standard deviation (*P <0.05).
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Figure 2: Inhibitory effects of collagen tripeptide, hyaluronan and collagen tripeptide/hyaluronan on osteoarthritis development. (A) Histologies of the medial femoral condylar cartilage stained with safranin-O. Arrow indicates cluster formation (original magnification ×100). (B) Appearance of safranin-O (×100) staining in the medial femoral condylar cartilage from a normal rabbit knee. (C) Osteoarthritis Research Society International (OARSI) {AU Query: Confirm definition} score for medial femoral condylar cartilage lesions in each group 5, 10 and 15 weeks after surgery. Ctp, collagen tripeptide; HA, hyaluronan. Data presented as mean ± standard deviation (*P <0.05).

Mentions: In the knees of the control group, safranin-O staining was severely reduced at an early stage; and as the number of injections progressed, the gradual loss of cartilage matrix was seen (Figure 2A). In some specimens of the control group, cluster formation was recognized 5, 10 and 15 weeks after injection. Conversely, treated groups had slightly reduced safranin-O staining at five injection points, and then slowly decreased at 10 and 15 weeks after surgery (Figure 2A). Cartilage structure was maintained until a comparatively late stage. Cluster formation was also recognized in some specimens of treated groups. Histological scores for the Ctp/HA group injected for 5 weeks were significantly decreased in comparison with the control group (Figure 2B). Ten weeks after surgery, the Ctp and HA groups exhibited significantly lower scores than the control group (Figure 2B). Furthermore, the HA group maintained a lower score than the control group at 15 weeks after surgery.


Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis.

Naraoka T, Ishibashi Y, Tsuda E, Yamamoto Y, Kusumi T, Toh S - Arthritis Res. Ther. (2013)

Inhibitory effects of collagen tripeptide, hyaluronan and collagen tripeptide/hyaluronan on osteoarthritis development. (A) Histologies of the medial femoral condylar cartilage stained with safranin-O. Arrow indicates cluster formation (original magnification ×100). (B) Appearance of safranin-O (×100) staining in the medial femoral condylar cartilage from a normal rabbit knee. (C) Osteoarthritis Research Society International (OARSI) {AU Query: Confirm definition} score for medial femoral condylar cartilage lesions in each group 5, 10 and 15 weeks after surgery. Ctp, collagen tripeptide; HA, hyaluronan. Data presented as mean ± standard deviation (*P <0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672813&req=5

Figure 2: Inhibitory effects of collagen tripeptide, hyaluronan and collagen tripeptide/hyaluronan on osteoarthritis development. (A) Histologies of the medial femoral condylar cartilage stained with safranin-O. Arrow indicates cluster formation (original magnification ×100). (B) Appearance of safranin-O (×100) staining in the medial femoral condylar cartilage from a normal rabbit knee. (C) Osteoarthritis Research Society International (OARSI) {AU Query: Confirm definition} score for medial femoral condylar cartilage lesions in each group 5, 10 and 15 weeks after surgery. Ctp, collagen tripeptide; HA, hyaluronan. Data presented as mean ± standard deviation (*P <0.05).
Mentions: In the knees of the control group, safranin-O staining was severely reduced at an early stage; and as the number of injections progressed, the gradual loss of cartilage matrix was seen (Figure 2A). In some specimens of the control group, cluster formation was recognized 5, 10 and 15 weeks after injection. Conversely, treated groups had slightly reduced safranin-O staining at five injection points, and then slowly decreased at 10 and 15 weeks after surgery (Figure 2A). Cartilage structure was maintained until a comparatively late stage. Cluster formation was also recognized in some specimens of treated groups. Histological scores for the Ctp/HA group injected for 5 weeks were significantly decreased in comparison with the control group (Figure 2B). Ten weeks after surgery, the Ctp and HA groups exhibited significantly lower scores than the control group (Figure 2B). Furthermore, the HA group maintained a lower score than the control group at 15 weeks after surgery.

Bottom Line: A Tukey's honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results.Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control.This effect appears to be exerted by promotion of type II collagen synthesis predominantly.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Collagen peptides have been reported to possess various biological activities for various cell types. The purposes of this study were, first, to examine the therapeutic effects of collagen tripeptide (Ctp) in rabbit osteoarthritis and, second, to explore a synergetic effect with hyaluronan (HA).

Methods: Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in 72 Japanese white rabbits and they were divided into four groups (control, Ctp, HA and Ctp/HA). Each material was injected weekly into the knee, and knee joint samples were collected 5, 10 and 15 weeks after surgery. Macroscopic and histomorphological analyses of cartilage were conducted. Expression of type II collagen and matrix metalloproteinase-13 was also analyzed immunohistochemically. A Tukey's honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results.

Results: All treatment groups exhibited slightly higher resistance to the progression of osteoarthritis than the control group macroscopically 15 weeks after surgery. Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control. Immunohistochemically, both Ctp-treated and Ctp/HA-treated groups had significantly increased type II collagen-positive chondrocytes at the fifth week after the surgery, although the numbers of matrix metalloproteinase-13-positive chondrocytes were not affected.

Conclusion: Periodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by anterior cruciate ligament transection in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly.

Show MeSH
Related in: MedlinePlus