Inducing articular cartilage phenotype in costochondral cells

Meghan K. Murphy, Grayson D. DuRaine, A Hari Reddi, Jerry C. Hu, Kyriacos A. Athanasiou

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Introduction: Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source.Methods: In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties.Results: Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1.Conclusions: Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage.

Original languageEnglish (US)
Article numberR214
JournalArthritis Research and Therapy
Volume15
Issue number6
DOIs
StatePublished - Dec 12 2013

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Chondroitin ABC Lyase
Articular Cartilage
Transforming Growth Factors
Hyaline Cartilage
Hydrostatic Pressure
Phenotype
Collagen
Proteins
Collagen Type II
Tensile Strength
Collagen Type I
Glycosaminoglycans
Cartilage
Joints
Pathology
Morbidity

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Inducing articular cartilage phenotype in costochondral cells. / Murphy, Meghan K.; DuRaine, Grayson D.; Reddi, A Hari; Hu, Jerry C.; Athanasiou, Kyriacos A.

In: Arthritis Research and Therapy, Vol. 15, No. 6, R214, 12.12.2013.

Research output: Contribution to journalArticle

Murphy, Meghan K. ; DuRaine, Grayson D. ; Reddi, A Hari ; Hu, Jerry C. ; Athanasiou, Kyriacos A. / Inducing articular cartilage phenotype in costochondral cells. In: Arthritis Research and Therapy. 2013 ; Vol. 15, No. 6.
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abstract = "Introduction: Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source.Methods: In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties.Results: Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175{\%} and glycosaminoglycan synthesis by 75{\%}, resulting in a nearly 200{\%} increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125{\%} increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30{\%} and tensile modulus by 45{\%}. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300{\%} and tensile strength by 320{\%}, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1.Conclusions: Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage.",
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