Improved Chondrogenic Capacity of Collagen Hydrogel-Expanded Chondrocytes

Sanz-Ramos, Patricia; Duart, Julio; Rodríguez-Goñi, María Victoria; Vicente-Pascual, Mikel; Dotor, Javier; Mora, Guillermo; Izal-Azcárate, Iñigo

doi:10.2106/jbjs.m.00271

Cited by 11 publications

(13 citation statements)

References 35 publications

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“…These results concur with those from our earlier research, in which we suggested that Alk-1 and Alk-5 are suitable candidates for the final effector of the response of chondrocytes to changes in substrate rigidity [8]. These two transmembrane proteins function as opposite receptors for TGFβ [19].…”

Section: Discussionsupporting

confidence: 93%

“…The average ± SD for every group (n = 6) is represented for passages 0, 2, 4, 6 and 8. D -We also used wildtype chondrocytes cultured onto hydrogels to which peptide was added after passage 4, when the cells had shown to increase the expression of Alk-1 receptor [8] and it would be desirable to inhibit TGFβ activity. *p < 0.05 for peptide-treated cells relative to the control cells in every passage.…”

Section: Inhibition Of Tgfβ In Hydrogel-cultured Alk-5 and Sh-alk-1 Cmentioning

confidence: 99%

“…We also used hydrogel expansion for the inhibition of TGFβ, adding P17 after the 4 th passage, when we had observed an increased level of Alk-1 [8]. At this point, the effect of inhibition was clear and significant, showing an increase in the expression of aggrecan and Col2, and a decrease in Col1 after the addition of the peptide.…”

Section: Inhibition Of Tgfβ In Hydrogel-cultured Alk-5 and Sh-alk-1 Cmentioning

confidence: 99%

“…In our laboratory, we used collagen hydrogels that support the culture of chondrocytes on substrates with low mechanical properties (in the range of pascals) [6,7]. We achieved an efficient expansion method that slowed down the dedifferentiation process that takes place when cells are cultured onto plastic [8]. The mechanisms responsible for this behavior of chondrocytes in the hydrogel culture are still unknown, but some clues have been found, such as the interesting pattern for transforming the growth factor β (TGFβ) receptors activin receptor-like kinase 1 and 5 (Alk-1 and Alk-5) [8].…”

Section: Introductionmentioning

confidence: 99%

“…We achieved an efficient expansion method that slowed down the dedifferentiation process that takes place when cells are cultured onto plastic [8]. The mechanisms responsible for this behavior of chondrocytes in the hydrogel culture are still unknown, but some clues have been found, such as the interesting pattern for transforming the growth factor β (TGFβ) receptors activin receptor-like kinase 1 and 5 (Alk-1 and Alk-5) [8]. We described an increase in the Alk-1 level in the plastic culture.…”

Section: Introductionmentioning

confidence: 99%

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The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

Sanz-Ramos

Dotor²,

Izal-Azcárate

2014

Cellular and Molecular Biology Letters

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Abbreviations used: Alk-1 -activin receptor-like kinase 1; Alk-5 -activin receptor-like kinase 5; FGFR3 -fibroblast growth factor receptor 3; FA -focal adhesions; MSCsmesenchymal stem cells; OA -osteoarthritis; TGFβ -transforming growth factor β; Col2 -type II collagen; Col1 -type I collagen; Col10 -type X collagen Abstract: We aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

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Section: Discussionsupporting

confidence: 93%

Section: Inhibition Of Tgfβ In Hydrogel-cultured Alk-5 and Sh-alk-1 Cmentioning

confidence: 99%

Section: Inhibition Of Tgfβ In Hydrogel-cultured Alk-5 and Sh-alk-1 Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

Sanz-Ramos

Dotor²,

Izal-Azcárate

2014

Cellular and Molecular Biology Letters

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Articular Cartilage Regeneration in Veterinary Medicine

Voga

Majdič

2022

Advances in Experimental Medicine and Biology

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Large Animal Models for Osteochondral Regeneration

Dias

Viegas

Carvalho

2018

Advances in Experimental Medicine and Biology

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Namely, in the last two decades, large animal models - small ruminants (sheep and goats), pigs, dogs and horses - have been used to study the physiopathology and to develop new therapeutic procedures to treat human clinical osteoarthritis. For that purpose, cartilage and/or osteochondral defects are generally performed in the stifle joint of selected large animal models at the condylar and trochlear femoral areas where spontaneous regeneration should be excluded. Experimental animal care and protection legislation and guideline documents of the US Food and Drug Administration, the American Society for Testing and Materials and the International Cartilage Repair Society should be followed, and also the specificities of the animal species used for these studies must be taken into account, such as the cartilage thickness of the selected defect localization, the defined cartilage critical size defect and the joint anatomy in view of the post-operative techniques to be performed to evaluate the chondral/osteochondral repair. In particular, in the articular cartilage regeneration and repair studies with animal models, the subchondral bone plate should always be taken into consideration. Pilot studies for chondral and osteochondral bone tissue engineering could apply short observational periods for evaluation of the cartilage regeneration up to 12 weeks post-operatively, but generally a 6- to 12-month follow-up period is used for these types of studies.

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Improved Chondrogenic Capacity of Collagen Hydrogel-Expanded Chondrocytes

Abstract: The study results favor the use of hydrogel-expanded cells over the traditional plastic-expanded cells for autologous chondrocyte implantation.

Cited by 11 publications

References 35 publications

The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

Articular Cartilage Regeneration in Veterinary Medicine

Large Animal Models for Osteochondral Regeneration

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