Osteoarthritis and cartilage · 2026
Modeling Progressive Pseudorheumatoid Arthropathy of Childhood: Disease Progression and Cartilage Pathology in CCN6 Knockout Sheep.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Ramirez Nereida J, Silveira Catrina J, Lunde-Young Raine, Huggins Shannon, Giering Jacob J, Mehrotra Dev R, Brisebois Henry E, Montagna Giulia, Sherman Kirby M, Falck Alyssa, Dahlstrom Cole B, Westhusin Mark E, Pryor Jane H, Albro Michael B, Gaddy Dana, Long Charles R, Warman Matthew L, Suva Larry J, Craft April M
Аннотация
OBJECTIVE: Progressive Pseudorheumatoid Arthropathy of Childhood (PPAC), also known as Progressive Pseudorheumatoid Dysplasia (PPRD), is an autosomal recessive disorder caused by loss-of-function variants in Cellular Communication Network Factor 6 (CCN6, aka, WISP3). Patients with PPAC are asymptomatic at birth but develop polyarticular arthropathy in childhood, requiring multiple arthroplasties before 30 years of age. Currently, no therapy prevents or delays PPAC progression. Furthermore, how loss of CCN6 affects joint development or homeostasis is unknown due to the unavailability of pre-symptomatic patient tissue and the absence of a phenotype in Ccn6 knockout (KO) mice.
METHODS: CCN6-KO sheep were generated, anticipating that a larger and longer-lived animal would better model human PPAC.
RESULTS: Juvenile KO sheep developed clinical signs of joint disease that worsened with age, and histologic examination of KO tissue revealed precocious cartilage damage. Additionally, KO cartilage differed from WT biomechanically, biochemically, and transcriptomically; with KO sheep cartilage sharing multiple transcriptomic features observed in cartilage derived from PPAC patient-induced pluripotent cell lines.
CONCLUSION: These data indicate CCN6-KO sheep recapitulate clinical, histological, and molecular features of PPAC, and can be used to elucidate disease mechanisms and test therapies.
METHODS: CCN6-KO sheep were generated, anticipating that a larger and longer-lived animal would better model human PPAC.
RESULTS: Juvenile KO sheep developed clinical signs of joint disease that worsened with age, and histologic examination of KO tissue revealed precocious cartilage damage. Additionally, KO cartilage differed from WT biomechanically, biochemically, and transcriptomically; with KO sheep cartilage sharing multiple transcriptomic features observed in cartilage derived from PPAC patient-induced pluripotent cell lines.
CONCLUSION: These data indicate CCN6-KO sheep recapitulate clinical, histological, and molecular features of PPAC, and can be used to elucidate disease mechanisms and test therapies.