Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig

Abstract Background Varieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was to determine whether this animal can serve as a more effective osteoarthritis model and explore the role of SDF-1/CXCR4 signaling pathway in the development of Osteoarthritis in animals. Methods Twenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection, and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. Synovium was taken out for stromal cell-derived factor-1 analysis. Results Histopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II revealed an apparent reduction in this marker in the chemical groups compared with the other groups. Conclusions These results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.

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Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig1

10.21203/rs.3.rs-24569/v2 ◽

2020 ◽

Author(s):

Di Jia ◽

Yinghong He ◽

Guofeng Cai ◽

Jiali Zheng ◽

Yuye Yang ◽

...

Keyword(s):

Stromal Cell ◽

Collagen Type ◽

The Other ◽

Cartilage Loss ◽

Type Ii ◽

Collagen Type Ii ◽

Matrix Metalloproteinase 3 ◽

Protein Levels ◽

Stromal Cell Derived Factor ◽

Chemical Groups

Abstract Background: Varieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was determine whether this animal can serve as a more effective osteoarthritis model.[A1] Methods: Twenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection [A2] , and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. [A3] Synovium was taken out for stromal cell-derived factor-1 analysis. Results: Histopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II[A4] and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II[A5] revealed an apparent reduction in this marker in the chemical groups compared with the other groups. Conclusions: These results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.

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Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig

10.21203/rs.3.rs-24569/v1 ◽

2020 ◽

Author(s):

Di Jia ◽

Yinghong He ◽

Guofeng Cai ◽

Jiali Zheng ◽

Yuye Yang ◽

...

Keyword(s):

Stromal Cell ◽

Collagen Type ◽

The Other ◽

Cartilage Loss ◽

Type Ii ◽

Collagen Type Ii ◽

Matrix Metalloproteinase 3 ◽

Protein Levels ◽

Stromal Cell Derived Factor ◽

Chemical Groups

Abstract Background: Varieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was determine whether this animal can serve as a more effective osteoarthritis model.Methods: Twenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection, and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. Synovium was taken out for stromal cell-derived factor-1 analysis. Results: Histopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II revealed an apparent reduction in this marker in the chemical groups compared with the other groups. Conclusions: These results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.

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Activin and Nodal Are Not Suitable Alternatives to TGFβ for Chondrogenic Differentiation of Mesenchymal Stem Cells

Cartilage ◽

10.1177/1947603516667585 ◽

2016 ◽

Vol 8 (4) ◽

pp. 432-438 ◽

Cited By ~ 1

Author(s):

Laurie M. G. de Kroon ◽

Esmeralda N. Blaney Davidson ◽

Roberto Narcisi ◽

Eric Farrell ◽

Peter M. van der Kraan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chondrogenic Differentiation ◽

Collagen Type ◽

Transforming Growth Factor ◽

Terminal Differentiation ◽

Transforming Growth Factor Β ◽

Type Ii ◽

Collagen Type Ii ◽

Protein Levels

Objective Previously, we demonstrated the importance of transforming growth factor-β (TGFβ)-activated SMAD2/3 signaling in chondrogenesis of bone marrow–derived mesenchymal stem cells (BMSCs). However, TGFβ also signals via the SMAD1/5/9 pathway, which is known to induce terminal differentiation of BMSCs. In this study, we investigated whether other SMAD2/3-activating ligands, Activin and Nodal, can induce chondrogenic differentiation of BMSCs without inducing terminal differentiation. Design Activation of SMAD2/3 signaling and chondrogenesis were evaluated in human BMSCs ( N = 3 donors) stimulated with TGFβ, Activin, or Nodal. SMAD2/3 activation was assessed by determining phosphorylated-SMAD2 (pSMAD2) protein levels and SMAD2/3-target gene expression of SERPINE1. Chondrogenesis was determined by ACAN and COL2A1 transcript analysis and histological examination of proteoglycans and collagen type II. Results Both Activin and TGFβ enhanced pSMAD2 and SERPINE1 expression compared to the control condition without growth factors, demonstrating activated SMAD2/3 signaling. pSMAD2 and SERPINE1 had a higher level of expression following stimulation with TGFβ than with Activin, while Nodal did not activate SMAD2/3 signaling. Of the 3 ligands tested, only TGFβ induced chondrogenic differentiation as shown by strongly increased transcript levels of ACAN and COL2A1 and positive histological staining of proteoglycans and collagen type II. Conclusions Even with concentrations up to 25 times higher than that of TGFβ, Activin and Nodal do not induce chondrogenic differentiation of BMSCs; thus, neither of the 2 ligands is an interesting alternative candidate for TGFβ to induce chondrogenesis without terminal differentiation. To obtain stable cartilage formation by BMSCs, future studies should decipher how TGFβ-induced terminal differentiation can be prevented.

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