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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.


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hCol1 reduces MMP13 levels in articular cartilage of mice following MLI.3 weeks post-injury (Sham or MLI), knee joints were harvested from mice and hypertrophic chondrocytes were analyzed by immunohistochemistry of MMP13 and ColX. Representative sagittal sections depict (A) MMP13 and (B) ColX stained chondrocytes (brown) with cell nuclei counterstained with hematoxylin (blue). Yellow dasted lines highlight the tide mark, separating calcified cartilage from uncalcified cartilage. Joint structures are labeled (F = femur, M = meniscus), and the black scale bar depicts 100μm.
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pone.0174705.g005: hCol1 reduces MMP13 levels in articular cartilage of mice following MLI.3 weeks post-injury (Sham or MLI), knee joints were harvested from mice and hypertrophic chondrocytes were analyzed by immunohistochemistry of MMP13 and ColX. Representative sagittal sections depict (A) MMP13 and (B) ColX stained chondrocytes (brown) with cell nuclei counterstained with hematoxylin (blue). Yellow dasted lines highlight the tide mark, separating calcified cartilage from uncalcified cartilage. Joint structures are labeled (F = femur, M = meniscus), and the black scale bar depicts 100μm.

Mentions: An important step in cartilage degeneration is the aberrant transition of articular chondrocytes into the hypertrophic state, an event marked by the expression of catabolic enzymes such as MMP13, and the marker of terminal hypertrophy, Type 10 Collagen (ColX). Accordingly, it is possible that the chondroprotective action of hCol1 documented in Figs 2–4 is associated with an inhibition of chondrocyte hypertrophy. To address this question, immunohistochemistry was performed to evaluate MMP13 and ColX protein levels in the articular cartilage. As expected, and indicative of chondrocyte hypertrophy, Control MLI mice had elevated levels of both MMP13 and ColX in the uncalcified cartilage compared to Control Sham mice at the 3 week time point (Fig 5A and 5B). Mice supplemented with HD hCol1 were protected from the MLI induced MMP13 staining in the uncalcified cartilage, suggesting that preservation of cartilage architecture in this group could in part be due to inhibion of matrix degeneration (Fig 5A). In contrast, ColX staining was not reduced in MLI mice supplemented with hCol1, indicating that hCol1 did not impact terminal chondrocyte hypertrophy (Fig 5B). Overall, no differences were observed in the calcified cartilage, as chondrocytes in this zone were all actively producing similar levels of both MMP13 and ColX (Fig 5A and 5B). It should be noted that at the 12 week time point, MLI joints from control-supplemented mice had lost most of the uncalcified cartilage and associated chondrocytes, making comparisons with the treated groups uninformative (data not shown). Together, these data suggest that mice supplemented with the HD hCol1 may have been protected from cartilage degeneration in part due to reduced MMP13 production by chondrocytes residing in the uncalcified cartilage.


Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis
hCol1 reduces MMP13 levels in articular cartilage of mice following MLI.3 weeks post-injury (Sham or MLI), knee joints were harvested from mice and hypertrophic chondrocytes were analyzed by immunohistochemistry of MMP13 and ColX. Representative sagittal sections depict (A) MMP13 and (B) ColX stained chondrocytes (brown) with cell nuclei counterstained with hematoxylin (blue). Yellow dasted lines highlight the tide mark, separating calcified cartilage from uncalcified cartilage. Joint structures are labeled (F = femur, M = meniscus), and the black scale bar depicts 100μm.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5383229&req=5

pone.0174705.g005: hCol1 reduces MMP13 levels in articular cartilage of mice following MLI.3 weeks post-injury (Sham or MLI), knee joints were harvested from mice and hypertrophic chondrocytes were analyzed by immunohistochemistry of MMP13 and ColX. Representative sagittal sections depict (A) MMP13 and (B) ColX stained chondrocytes (brown) with cell nuclei counterstained with hematoxylin (blue). Yellow dasted lines highlight the tide mark, separating calcified cartilage from uncalcified cartilage. Joint structures are labeled (F = femur, M = meniscus), and the black scale bar depicts 100μm.
Mentions: An important step in cartilage degeneration is the aberrant transition of articular chondrocytes into the hypertrophic state, an event marked by the expression of catabolic enzymes such as MMP13, and the marker of terminal hypertrophy, Type 10 Collagen (ColX). Accordingly, it is possible that the chondroprotective action of hCol1 documented in Figs 2–4 is associated with an inhibition of chondrocyte hypertrophy. To address this question, immunohistochemistry was performed to evaluate MMP13 and ColX protein levels in the articular cartilage. As expected, and indicative of chondrocyte hypertrophy, Control MLI mice had elevated levels of both MMP13 and ColX in the uncalcified cartilage compared to Control Sham mice at the 3 week time point (Fig 5A and 5B). Mice supplemented with HD hCol1 were protected from the MLI induced MMP13 staining in the uncalcified cartilage, suggesting that preservation of cartilage architecture in this group could in part be due to inhibion of matrix degeneration (Fig 5A). In contrast, ColX staining was not reduced in MLI mice supplemented with hCol1, indicating that hCol1 did not impact terminal chondrocyte hypertrophy (Fig 5B). Overall, no differences were observed in the calcified cartilage, as chondrocytes in this zone were all actively producing similar levels of both MMP13 and ColX (Fig 5A and 5B). It should be noted that at the 12 week time point, MLI joints from control-supplemented mice had lost most of the uncalcified cartilage and associated chondrocytes, making comparisons with the treated groups uninformative (data not shown). Together, these data suggest that mice supplemented with the HD hCol1 may have been protected from cartilage degeneration in part due to reduced MMP13 production by chondrocytes residing in the uncalcified cartilage.

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