Chondrocyte clusters adjacent to sites of cartilage degeneration have characteristics of progenitor cells

Abstract

The purpose of this study was to investigate the site-specific expression pattern and the role of chondrocyte clusters in human OA knee. Cartilage explants were obtained from 45 varus knees of medial and lateral femoral condyle undergoing total knee replacement surgery. Cartilage degeneration, number of chondrocytes, and the cell arrangement were evaluated by live/dead assay and immunohistochemical analyses with antibodies of STRO-1, FGF2, and Ki-67. Chondrocytes from medial and lateral femoral condyle were cultured to compare the potential of cell proliferation and production of cartilaginous nodules. Finally, cartilage tissue from medial femoral condyle, which included cartilage cleft with chondrocyte clusters, was observed the histological alternation. As the results, chondrocyte density adjacent to severe cartilage degeneration was highest, whereas chondrocytes in lateral femoral condyle displayed low density with single type of cells. Over 80% of these chondrocyte clusters were survived, expressing STRO-1, FGF2, and Ki-67. Furthermore, chondrocyte clusters proliferated faster and produced more cartilaginous nodules than single type of chondrocytes. Cartilage clefts involving numerous chondrocyte clusters were filled with extracellular matrix during organ culture. In conclusion, chondrocyte clusters adjacent to severe cartilage degeneration have shown completely specific characteristics with progenitor and proliferative potential. Regulating chondrocyte clusters may offer new approaches to cartilage repair and OA therapy in the future.

Statistical image analysis and escort histograms in characterization of articular cartilage repair in a skeleton animal model

“…Again, as it was for Hellinger distance, Shannon entropy can serve as a auxiliary tool to infer effectiveness of medical treatment from a digital image of histological samples. In particular, using Shannon entropy of escort histograms we confirm formation of clusters [21][22][23][24] already observed in Ref [3] and indicate cf. Fig 6 for a given staining of a histological sample a color component of an RGB image most suitable for its verification.…”

Statistical image analysis and escort histograms in characterization of articular cartilage repair in a skeleton animal model

“…Again, as it was for Hellinger distance, Shannon entropy can serve as a auxiliary tool to infer effectiveness of medical treatment from a digital image of histological samples. In particular, using Shannon entropy of escort histograms we confirm formation of clusters [21][22][23][24] already observed in Ref [3] and indicate cf. Fig 6 for a given staining of a histological sample a color component of an RGB image most suitable for its verification.…”

Cell Clusters Are Indicative of Stem Cell Activity in the Degenerate Intervertebral Disc: Can Their Properties Be Manipulated to Improve Intrinsic Repair of the Disc?

“…These cell clusters have similar morphologies to the cell clusters observed in the inner AF in experimental disc degeneration in the present study and synthesize progenitor/MSC markers such as Sox9 and Stro-1 [232,233]. In articular cartilage and meniscus, it has been suggested that these cell clusters represent a reparative response by adult progenitor cell populations located adjacent to surface fibrillations [234]. Such OA cell clusters also express the HS-proteoglycan perlecan [235], which is induced by Sox9 gene expression [236].…”

Ablation of Perlecan Domain 1 Heparan Sulfate Reduces Progressive Cartilage Degradation, Synovitis, and Osteophyte Size in a Preclinical Model of Posttraumatic Osteoarthritis

“…The levels of HSPG-2, FGF-2, FGF-18, FGFR-1, and FGFR-3 were consistently decreased in OA cartilage lesions after DMM, whereas staining was maintained in the peripheral cartilage and osteophytes and increased in the synovium. Such tissue and topographic differences have been previously reported in human OA, in which, despite increased FGF-2 levels in the synovium and synovial fluid (40,41), the levels of FGF-2 protein (and mRNA) in OA cartilage have been found to vary between patients according to disease severity and according to whether lesion, perilesion, distant, or marginal/osteophyte tissue is examined (42)(43)(44). The single report on chondrocyte HSPG-2 in OA describes increased staining surrounding chondrocyte clusters only in the perilesion cartilage (45), where FGF-2 is also most strongly localized (42).…”

Statistical image analysis and escort histograms in characterization of articular cartilage repair in a skeleton animal model

“…Again, as it was for Hellinger distance, Shannon entropy can serve as a auxiliary tool to infer effectiveness of medical treatment from a digital image of histological samples. In particular, using Shannon entropy of escort histograms we confirm formation of clusters [21][22][23][24] already observed in Ref [3] and indicate cf. Fig 6 for a given staining of a histological sample a color component of an RGB image most suitable for its verification.…”

Cell Clusters Are Indicative of Stem Cell Activity in the Degenerate Intervertebral Disc: Can Their Properties Be Manipulated to Improve Intrinsic Repair of the Disc?

“…These cell clusters have similar morphologies to the cell clusters observed in the inner AF in experimental disc degeneration in the present study and synthesize progenitor/MSC markers such as Sox9 and Stro-1 [232,233]. In articular cartilage and meniscus, it has been suggested that these cell clusters represent a reparative response by adult progenitor cell populations located adjacent to surface fibrillations [234]. Such OA cell clusters also express the HS-proteoglycan perlecan [235], which is induced by Sox9 gene expression [236].…”

Ablation of Perlecan Domain 1 Heparan Sulfate Reduces Progressive Cartilage Degradation, Synovitis, and Osteophyte Size in a Preclinical Model of Posttraumatic Osteoarthritis

“…The levels of HSPG-2, FGF-2, FGF-18, FGFR-1, and FGFR-3 were consistently decreased in OA cartilage lesions after DMM, whereas staining was maintained in the peripheral cartilage and osteophytes and increased in the synovium. Such tissue and topographic differences have been previously reported in human OA, in which, despite increased FGF-2 levels in the synovium and synovial fluid (40,41), the levels of FGF-2 protein (and mRNA) in OA cartilage have been found to vary between patients according to disease severity and according to whether lesion, perilesion, distant, or marginal/osteophyte tissue is examined (42)(43)(44). The single report on chondrocyte HSPG-2 in OA describes increased staining surrounding chondrocyte clusters only in the perilesion cartilage (45), where FGF-2 is also most strongly localized (42).…”

Statistical image analysis and escort histograms in characterization of articular cartilage repair in a skeleton animal model

“…Again, as it was for Hellinger distance, Shannon entropy can serve as a auxiliary tool to infer effectiveness of medical treatment from a digital image of histological samples. In particular, using Shannon entropy of escort histograms we confirm formation of clusters [21][22][23][24] already observed in Ref [3] and indicate cf. Fig 6 for a given staining of a histological sample a color component of an RGB image most suitable for its verification.…”

Cell Clusters Are Indicative of Stem Cell Activity in the Degenerate Intervertebral Disc: Can Their Properties Be Manipulated to Improve Intrinsic Repair of the Disc?

“…These cell clusters have similar morphologies to the cell clusters observed in the inner AF in experimental disc degeneration in the present study and synthesize progenitor/MSC markers such as Sox9 and Stro-1 [232,233]. In articular cartilage and meniscus, it has been suggested that these cell clusters represent a reparative response by adult progenitor cell populations located adjacent to surface fibrillations [234]. Such OA cell clusters also express the HS-proteoglycan perlecan [235], which is induced by Sox9 gene expression [236].…”

Ablation of Perlecan Domain 1 Heparan Sulfate Reduces Progressive Cartilage Degradation, Synovitis, and Osteophyte Size in a Preclinical Model of Posttraumatic Osteoarthritis

“…The levels of HSPG-2, FGF-2, FGF-18, FGFR-1, and FGFR-3 were consistently decreased in OA cartilage lesions after DMM, whereas staining was maintained in the peripheral cartilage and osteophytes and increased in the synovium. Such tissue and topographic differences have been previously reported in human OA, in which, despite increased FGF-2 levels in the synovium and synovial fluid (40,41), the levels of FGF-2 protein (and mRNA) in OA cartilage have been found to vary between patients according to disease severity and according to whether lesion, perilesion, distant, or marginal/osteophyte tissue is examined (42)(43)(44). The single report on chondrocyte HSPG-2 in OA describes increased staining surrounding chondrocyte clusters only in the perilesion cartilage (45), where FGF-2 is also most strongly localized (42).…”