Unraveling sex-specific risks of knee osteoarthritis before menopause: Do sex differences start early in life?

Hernandez, Paula A.; Bradford, John Churchill; Brahmachary, Priyanka; Ulman, Sophia; Robinson, Jennifer L.; June, Ronald K.; Cucchiarini, Magali

doi:10.1016/j.joca.2024.04.015

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2024

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Cited by 3 publications

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Association between sarcopenic obesity and osteoarthritis: The potential mediating role of insulin resistance

Li,

Yin,

Zhao

et al. 2024

Experimental Gerontology

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Association between sarcopenic obesity and osteoarthritis: The potential mediating role of insulin resistance

Li,

Yin,

Zhao

et al. 2024

Experimental Gerontology

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From cartilage to culture: Opportunities for unraveling the complexities of osteoarthritis through sex and gender

Maerz,

Schiphof

2024

Osteoarthritis and Cartilage

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Transcriptomic changes during the replicative senescence of human articular chondrocytes

Atasoy-Zeybek,

Hawse,

Nagelli

et al. 2024

Preprint

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Objective Aging is a major risk factor for OA, but the specific mechanisms underlying this connection remain unclear. Although chondrocytes rarely divide in adult articular cartilage, they undergo replicative senescence in vitro which provides an opportunity to study changes related to aging under controlled laboratory conditions. Methods Cartilage was recovered from two knees with OA and one normal knee. Chondrocyte cultures were established and sub-cultured until their Hayflick limit. Bulk RNA sequencing on early- and late-passage human articular chondrocytes allowed identification of transcriptomic changes associated with cellular aging. Results One male (80 years old) and one female (72 years old) patient provided OA cartilage. The donor of normal chondrocytes was a 26-year old male. Early passage chondrocytes from the two OA samples already had the phenotype of senescing cells, unlike normal chondrocytes. Nevertheless, all three chondrocyte cultures underwent 30 population doublings before replicative exhaustion, by which point all cells displayed a senescent phenotype. During this process, the cells lost their ability to form cartilaginous pellets. Differentially expressed genes (DEGs) analysis confirmed distinct transcriptomic profiles between early- and late-passage chondrocytes, as well as between cells isolated from normal and OA cartilage. Various changes in expression of genes related to cartilage matrix synthesis, degradation, inflammation and the senescence-associated secretory phenotype (SASP) were noted. Conclusions Although only a small pilot study, its data suggest that a larger and deeper study of the molecular and metabolic events accompanying the senescence of chondrocytes could provide important insights into the pathobiology of OA.

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Unraveling sex-specific risks of knee osteoarthritis before menopause: Do sex differences start early in life?

Cited by 3 publications

References 162 publications

Association between sarcopenic obesity and osteoarthritis: The potential mediating role of insulin resistance

Association between sarcopenic obesity and osteoarthritis: The potential mediating role of insulin resistance

From cartilage to culture: Opportunities for unraveling the complexities of osteoarthritis through sex and gender

Transcriptomic changes during the replicative senescence of human articular chondrocytes

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