Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and antiinflammatory in murine posttraumatic osteoarthritis

Qurratul Ain Dar, Eric M. Schott, Sarah E. Catheline, Robert D. Maynard, Zhaoyang Liu, Fadia Kamal, Christopher W. Farnsworth, John P. Ketz, Robert A. Mooney, Matthew J. Hilton, Jennifer H. Jonason, Janne Prawitt, Michael J. Zuscik

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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.

Original languageEnglish (US)
Article numbere0174705
JournalPLoS One
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

osteoarthritis
Chondrocytes
Collagen Type I
Osteoarthritis
chondrocytes
knees
collagen
mouth
Anti-Inflammatory Agents
Hydroxyproline
Cartilage
Tissue
mice
Dietary supplements
hydroxyproline
Knee
Messenger RNA
Wounds and Injuries
joints (animal)
cartilage

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dar, Qurratul Ain ; Schott, Eric M. ; Catheline, Sarah E. ; Maynard, Robert D. ; Liu, Zhaoyang ; Kamal, Fadia ; Farnsworth, Christopher W. ; Ketz, John P. ; Mooney, Robert A. ; Hilton, Matthew J. ; Jonason, Jennifer H. ; Prawitt, Janne ; Zuscik, Michael J. / Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and antiinflammatory in murine posttraumatic osteoarthritis. In: PLoS One. 2017 ; Vol. 12, No. 4.
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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.",
author = "Dar, {Qurratul Ain} and Schott, {Eric M.} and Catheline, {Sarah E.} and Maynard, {Robert D.} and Zhaoyang Liu and Fadia Kamal and Farnsworth, {Christopher W.} and Ketz, {John P.} and Mooney, {Robert A.} and Hilton, {Matthew J.} and Jonason, {Jennifer H.} and Janne Prawitt and Zuscik, {Michael J.}",
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Dar, QA, Schott, EM, Catheline, SE, Maynard, RD, Liu, Z, Kamal, F, Farnsworth, CW, Ketz, JP, Mooney, RA, Hilton, MJ, Jonason, JH, Prawitt, J & Zuscik, MJ 2017, 'Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and antiinflammatory in murine posttraumatic osteoarthritis', PLoS One, vol. 12, no. 4, e0174705. https://doi.org/10.1371/journal.pone.0174705

Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and antiinflammatory in murine posttraumatic osteoarthritis. / Dar, Qurratul Ain; Schott, Eric M.; Catheline, Sarah E.; Maynard, Robert D.; Liu, Zhaoyang; Kamal, Fadia; Farnsworth, Christopher W.; Ketz, John P.; Mooney, Robert A.; Hilton, Matthew J.; Jonason, Jennifer H.; Prawitt, Janne; Zuscik, Michael J.

In: PLoS One, Vol. 12, No. 4, e0174705, 01.04.2017.

Research output: Contribution to journalArticle

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AU - Dar, Qurratul Ain

AU - Schott, Eric M.

AU - Catheline, Sarah E.

AU - Maynard, Robert D.

AU - Liu, Zhaoyang

AU - Kamal, Fadia

AU - Farnsworth, Christopher W.

AU - Ketz, John P.

AU - Mooney, Robert A.

AU - Hilton, Matthew J.

AU - Jonason, Jennifer H.

AU - Prawitt, Janne

AU - Zuscik, Michael J.

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N2 - 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.

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