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Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis

View Article: PubMed Central - PubMed

ABSTRACT

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed type 1 collagen (hCol1) preparation has been reported to reduce pain in human OA and support a positive influence on chondrocyte function. To evaluate the tissue and cellular basis for these effects, we examined the impact of orally administered hCol1 in a model of posttraumatic OA (PTOA). In addition to standard chow, male C57BL/6J mice were provided a daily oral dietary supplement of hCol1 and a meniscal-ligamentous injury was induced on the right knee. At various time points post-injury, hydroxyproline (hProline) assays were performed on blood samples to confirm hCol1 delivery, and joints were harvested for tissue and molecular analyses were performed, including histomorphometry, OARSI and synovial scoring, immunohistochemistry and mRNA expression studies. Confirming ingestion of the supplements, serum hProline levels were elevated in experimental mice administered hCol1. In the hCol1 supplemented mice, chondroprotective effects were observed in injured knee joints, with dose-dependent increases in cartilage area, chondrocyte number and proteoglycan matrix at 3 and 12 weeks post-injury. Preservation of cartilage and increased chondrocyte numbers correlated with reductions in MMP13 protein levels and apoptosis, respectively. Supplemented mice also displayed reduced synovial hyperplasia that paralleled a reduction in Tnf mRNA, suggesting an anti-inflammatory effect. These findings establish that in the context of murine knee PTOA, daily oral consumption of hCol1 is chondroprotective, anti-apoptotic in articular chondrocytes, and anti-inflammatory. While the underlying mechanism driving these effects is yet to be determined, these findings provide the first tissue and cellular level information explaining the already published evidence of symptom relief supported by hCol1 in human knee OA. These results suggest that oral consumption of hCol1 is disease modifying in the context of PTOA.

No MeSH data available.


Related in: MedlinePlus

Synovial hyperplasia is reduced in mice supplemented with hCol1.(A) Tissue sections stained with Safranin O/Fast Green were used to examine the synovium. Representative 40x sagittal sections from Sham and MLI joints of mice supplemented with Control (vehicle, hazelnut cream), LD hCol1 or HD hCol1 that were harvested at 3 and 12 weeks post-injury are depicted. Joint structures are labeled (F = femur, M = meniscus, T = tibia), and synovial membranes are demarcated with black arrows. The red line highlights the thickness of hyperplastic synovium in the Control MLI section and the black scale bar depicts 100μm. A synovial scoring method was also employed to quantify synovial hyperplasia at both 3 weeks (B) and 12 weeks (C) post-injury. Symbols (○) represent the average Synovial Score for each joint based on scoring of 3 sections/joint by four observers. Bars represent the average Synovial Score per experimental group (± standard deviation, N = 5–8 joints). Significant differences between experimental groups were identified via a Kruskal-Wallis Test with a Dunn’s multiple comparisons post-test (*p<0.05, **p<0.01, ***p<0.001 compared to Control Sham).
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pone.0174705.g007: Synovial hyperplasia is reduced in mice supplemented with hCol1.(A) Tissue sections stained with Safranin O/Fast Green were used to examine the synovium. Representative 40x sagittal sections from Sham and MLI joints of mice supplemented with Control (vehicle, hazelnut cream), LD hCol1 or HD hCol1 that were harvested at 3 and 12 weeks post-injury are depicted. Joint structures are labeled (F = femur, M = meniscus, T = tibia), and synovial membranes are demarcated with black arrows. The red line highlights the thickness of hyperplastic synovium in the Control MLI section and the black scale bar depicts 100μm. A synovial scoring method was also employed to quantify synovial hyperplasia at both 3 weeks (B) and 12 weeks (C) post-injury. Symbols (○) represent the average Synovial Score for each joint based on scoring of 3 sections/joint by four observers. Bars represent the average Synovial Score per experimental group (± standard deviation, N = 5–8 joints). Significant differences between experimental groups were identified via a Kruskal-Wallis Test with a Dunn’s multiple comparisons post-test (*p<0.05, **p<0.01, ***p<0.001 compared to Control Sham).

Mentions: The marked preservation of matrix-producing chondrocytes post-MLI in hCol1 supplemented mice begged for subsequent investigation of the impact of hCol1 on inflammatory synovial changes that are known to contribute to chondrocyte death following joint injury [32, 33]. Comparison of representative Safranin O/Fast Green stained sagittal knee joint sections revealed an apparent reduction in the severity of synovial hyperplasia in mice provided the hCol1 supplements. At both 3 and 12 weeks post-MLI, synovial thickness was increased compared to Control Sham joints, while mice provided hCol1 were protected from MLI-induced hyperplastic synovial change (Fig 7A). Synovial phenotypes were further investigated using a synovial scoring method, revealing significant effects in mice provided hCol1 supplements that were consistent with the representative histology. As expected, MLI induced a significant increase in synovial score (i.e. more robust synovial hyperplasia) at both 3 weeks (Fig 7B) and 12 weeks (Fig 7C) post-MLI. At 3 weeks, synovial scores trended toward a reduction (improvement) in the MLI groups that were supplemented with hCol1 (Fig 7B). Comparatively, at 12 weeks post-MLI, the synovium in mice from the HD hCol1 group was significantly less hyperplastic, suggesting that hCol1 supplements effectively reduced synovial/joint inflammation that is present in PTOA.


Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis
Synovial hyperplasia is reduced in mice supplemented with hCol1.(A) Tissue sections stained with Safranin O/Fast Green were used to examine the synovium. Representative 40x sagittal sections from Sham and MLI joints of mice supplemented with Control (vehicle, hazelnut cream), LD hCol1 or HD hCol1 that were harvested at 3 and 12 weeks post-injury are depicted. Joint structures are labeled (F = femur, M = meniscus, T = tibia), and synovial membranes are demarcated with black arrows. The red line highlights the thickness of hyperplastic synovium in the Control MLI section and the black scale bar depicts 100μm. A synovial scoring method was also employed to quantify synovial hyperplasia at both 3 weeks (B) and 12 weeks (C) post-injury. Symbols (○) represent the average Synovial Score for each joint based on scoring of 3 sections/joint by four observers. Bars represent the average Synovial Score per experimental group (± standard deviation, N = 5–8 joints). Significant differences between experimental groups were identified via a Kruskal-Wallis Test with a Dunn’s multiple comparisons post-test (*p<0.05, **p<0.01, ***p<0.001 compared to Control Sham).
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pone.0174705.g007: Synovial hyperplasia is reduced in mice supplemented with hCol1.(A) Tissue sections stained with Safranin O/Fast Green were used to examine the synovium. Representative 40x sagittal sections from Sham and MLI joints of mice supplemented with Control (vehicle, hazelnut cream), LD hCol1 or HD hCol1 that were harvested at 3 and 12 weeks post-injury are depicted. Joint structures are labeled (F = femur, M = meniscus, T = tibia), and synovial membranes are demarcated with black arrows. The red line highlights the thickness of hyperplastic synovium in the Control MLI section and the black scale bar depicts 100μm. A synovial scoring method was also employed to quantify synovial hyperplasia at both 3 weeks (B) and 12 weeks (C) post-injury. Symbols (○) represent the average Synovial Score for each joint based on scoring of 3 sections/joint by four observers. Bars represent the average Synovial Score per experimental group (± standard deviation, N = 5–8 joints). Significant differences between experimental groups were identified via a Kruskal-Wallis Test with a Dunn’s multiple comparisons post-test (*p<0.05, **p<0.01, ***p<0.001 compared to Control Sham).
Mentions: The marked preservation of matrix-producing chondrocytes post-MLI in hCol1 supplemented mice begged for subsequent investigation of the impact of hCol1 on inflammatory synovial changes that are known to contribute to chondrocyte death following joint injury [32, 33]. Comparison of representative Safranin O/Fast Green stained sagittal knee joint sections revealed an apparent reduction in the severity of synovial hyperplasia in mice provided the hCol1 supplements. At both 3 and 12 weeks post-MLI, synovial thickness was increased compared to Control Sham joints, while mice provided hCol1 were protected from MLI-induced hyperplastic synovial change (Fig 7A). Synovial phenotypes were further investigated using a synovial scoring method, revealing significant effects in mice provided hCol1 supplements that were consistent with the representative histology. As expected, MLI induced a significant increase in synovial score (i.e. more robust synovial hyperplasia) at both 3 weeks (Fig 7B) and 12 weeks (Fig 7C) post-MLI. At 3 weeks, synovial scores trended toward a reduction (improvement) in the MLI groups that were supplemented with hCol1 (Fig 7B). Comparatively, at 12 weeks post-MLI, the synovium in mice from the HD hCol1 group was significantly less hyperplastic, suggesting that hCol1 supplements effectively reduced synovial/joint inflammation that is present in PTOA.

View Article: PubMed Central - PubMed

ABSTRACT

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed type 1 collagen (hCol1) preparation has been reported to reduce pain in human OA and support a positive influence on chondrocyte function. To evaluate the tissue and cellular basis for these effects, we examined the impact of orally administered hCol1 in a model of posttraumatic OA (PTOA). In addition to standard chow, male C57BL/6J mice were provided a daily oral dietary supplement of hCol1 and a meniscal-ligamentous injury was induced on the right knee. At various time points post-injury, hydroxyproline (hProline) assays were performed on blood samples to confirm hCol1 delivery, and joints were harvested for tissue and molecular analyses were performed, including histomorphometry, OARSI and synovial scoring, immunohistochemistry and mRNA expression studies. Confirming ingestion of the supplements, serum hProline levels were elevated in experimental mice administered hCol1. In the hCol1 supplemented mice, chondroprotective effects were observed in injured knee joints, with dose-dependent increases in cartilage area, chondrocyte number and proteoglycan matrix at 3 and 12 weeks post-injury. Preservation of cartilage and increased chondrocyte numbers correlated with reductions in MMP13 protein levels and apoptosis, respectively. Supplemented mice also displayed reduced synovial hyperplasia that paralleled a reduction in Tnf mRNA, suggesting an anti-inflammatory effect. These findings establish that in the context of murine knee PTOA, daily oral consumption of hCol1 is chondroprotective, anti-apoptotic in articular chondrocytes, and anti-inflammatory. While the underlying mechanism driving these effects is yet to be determined, these findings provide the first tissue and cellular level information explaining the already published evidence of symptom relief supported by hCol1 in human knee OA. These results suggest that oral consumption of hCol1 is disease modifying in the context of PTOA.

No MeSH data available.


Related in: MedlinePlus