ISSN 2412-4036 (print)
ISSN 2713-1823 (online)

Early osteoarthritis in heritable disorders of connective tissue: TGF-β-associated endophenotypes and subchondral bone remodeling

A.S. Rudoy

Republican Scientific and Practical Center “Cardiology”, Minsk, Republic of Belarus

ABSTRACT. Early osteoarthritis (OA) developing in young individuals is increasingly recognized as one of the clinical manifestations of heritable disorders of connective tissue (HDCTs). In contrast to age-associated osteoarthritis, degenerative joint changes in HDCTs arise in the context of primary defects of the extracellular matrix, impaired mechanotransduction, and dysregulation of tissue-remodeling signaling pathways, particularly transforming growth factor-β (TGF-β). This review discusses the hypothesis of distinct endophenotypes of early OA in HDCTs, including a fibrotic endophenotype (predominantly associated with Marfan syndrome), and osteopenic and mixed endophenotypes, more commonly observed in hypermobility-related conditions such as the hypermobile type of Ehlers–Danlos syndrome. Particular emphasis is placed on the role of subchondral bone as an active pathogenic compartment and on TGF-β-mediated transdifferentiation of resident fibroblasts into α-smooth muscle actin (α-SMA)-positive myofibroblasts, which may promote the formation of a functionally compromised collagen matrix. Phenotypic stratification of early OA in HDCTs is considered a prerequisite for a personalized approach to diagnosis and management in this patient population.

For citation: Rudoy AS. Early osteoarthritis in heritable disorders of connective tissue: TGF-β-associated endophenotypes and subchondral bone remodeling. Therapy (Moscow). 2026;12(5S):104–115.
https://doi.org/10.18565/therapy.2026.5-s5.104-115

Ключевые слова

osteoarthritis
heritable connective tissue disorders
undifferentiated connective tissue dysplasia
Marfan syndrome
joint hypermobility syndrome
transforming growth factor-β
subchondral bone
Ehlers–Danlos syndrome
fibroblasts
α-smooth muscle actin-positive myofibroblasts
collagen

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Об авторах / Для корреспонденции

Andrei S. Rudoy, MD, Dr. Sci. (Medicine), professor, physician at the Republican Center for Pulmonary Hypertension of the Department of consultative work and preventive cardiology, Republican Scientific and Practical Center “Cardiology”, Minsk, Republic of Belarus.
E-mail: andrewrudoj@gmail.com
ORCID: https://orcid.org/0000-0001-9010-0264. Scopus ID: 57196065075

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