Donor ethnicity, sex, and age impact chondrogenic re-differentiation capacity: a multi-demographic study of human articular chondrocytes in vitro

ABSTRACT

To unravel causes of disparities in osteoarthritis (OA) prevalence and to improve cell-based cartilage repair treatments, there is need to investigate the multifactorial impact of patient demographics on a biophysiological level. In this study, we systematically analyse single- and multi-demographic impact on in vitro chondrogenic re-differentiation capacity of human articular chondrocytes (hACs), specifically of an Aotearoa-New Zealand (NZ) patient cohort which displays unique demographic diversity. HACs were isolated from 14 NZ donors with distinct demographics (ethnicity: indigenous Māori vs European descendant Pākehā; sex; age 18–24 vs 25–30 yrs). In vitro chondrogenic re-differentiation capacity of donor chondrocytes was assessed through quantifications of cartilage matrix deposition (GAG, DNA, GAG/DNA) and by histological visualisation. Isolated chondrocytes ranged from low chondrogenic re-differentiation capacity, characterised by fibrocartilage tissue deposition, to high re-differentiation capacity to deposit GAG-rich tissue. Age-related reduction in GAG/DNA content was detected while no impact of ethnicity or sex was observed. Multi-demographic analysis revealed reduced GAG deposition in Māori male (compared to Māori female), and Māori (18–24 yrs) compared to Māori (25–30 yrs) and Pākehā (18–24 yrs) within our cohort. Multi-demographic analysis is a promising strategy to understand disparities in OA prevalence in patient cohorts and can help guide development of cell-based strategies for diverse patient populations.

KEYWORDS:

• Osteoarthritis
• chondrocytes
• 3D cell culture
• in vitro chondrogenesis
• ethnicity
• age
• sex
• indigenous
• Māori
• Pākehā

Acknowledgements

The authors are grateful to Andrew Vincent, orthopaedic surgeon at the Forte health clinic in Christchurch, who collected cartilage tissues during surgical procedures. The authors are furthermore grateful to the patients who gave consent for cartilage tissue collection.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

GL, LV, VL and TW contributed to the conception and design of the article. Experiments, analysis and interpretation of the data were performed by GL, LV and VL. The article was written by LV and VL. All authors critically revised and edited the manuscript draft and approved the final manuscript.

Additional information

Funding

The authors acknowledge funding by Health Research Council of New Zealand Emerging Researcher First Grants 19/679 (GL), Explorer 21/802 (GL), and the University of Otago Health Science Postdoctoral Fellowship (GL).