A Novel Concept of Tissue Micro-Instability as the Underlying Mechanism of Osteophytosis in Human Knee Osteoarthritis

Volkov, A.; Lyalina, V.; Eshmotova, G.; Serejnikova, N.; Petrova, S.; Airapetov, G.; Parshina, E.; Zalygin, A.; Belitskaya, E.; Oleinikov, V.; Bonartsev, A.; Borisovskaya, S.; Zagorodny, N.; Prizov, A.

Авторы: Volkov Alexey, Lyalina Vera, Eshmotova Gulnara, Serejnikova Natalia, Petrova Sofia, Airapetov George, Parshina Evgeniya, Zalygin Anton, Belitskaya Ekaterina, Oleinikov Vladimir, Bonartsev Anton, Borisovskaya Svetlana, Zagorodny Nikolai, Prizov Alexey
Журнал: BIOMEDICINES
Том: 14
Номер: 283
Год издания: 2026
Первая страница: 1
Последняя страница: 24
DOI: 10.3390/biomedicines14020283
Аннотация: Osteophytes (OPs) are a diagnostic hallmark of osteoarthritis (OA). However, the mechanismsunderlying their initiation and their relationship with early subchondral bonechanges remain poorly understood. Existing research primarily relies on animal modelsand late-stage OA tissue, leaving the initial morphological events leading to OP formationunclear. Background/Objectives: This study aimed to identify early changes in the subchondralbone as a key trigger for OP initiation in human OA through a comprehensivehistological analysis of the subchondral area, including its peripheral regions. Methods:We conducted an extensive histological examination of full-section human tibial plateaus,including load-bearing and non-load-bearing compartments, obtained from patients withearly and late stages of OA. Results: Our data demonstrate that subchondral bone changes,including osteoporosis, osteosclerosis, and microcracks, begin at the pre-chondropathicstage alongside microscopically intact cartilage. We identified a previously undescribedzone on the vertical wall of the tibial condyle (the VEPLS zone), characterized by reducedcalcium content in the cortical plate and the persistence of embryonic cartilage, making itmorphologically vulnerable. The first event in OP formation is microcracks in the corticalangle and the adjacent subchondral trabecula. These injuries initiate reparative osteogenesis,which, under continuous traumatic load (presumably shear forces due to jointinstability), becomes insufficient, leading to cortical angle protrusion and OP formation.OP growth is accompanied by the deformation of the VEPLS zone cortical plate, causingvascular impairment and exacerbating bone weakness. Conclusions: Based on our findings,we propose the concept of tissue micro-instability. This concept posits that osteophytosisresults from chronic microcracks and failed bone regeneration in vulnerable subchondralstructures, induced by joint instability. We define an OP as a pathological outgrowth arisingfrom this tissue micro-instability. Our study highlights the critical role of the peripheralsubchondral area, particularly the VEPLS zone, in OA pathogenesis.
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A Novel Concept of Tissue Micro-Instability as the Underlying Mechanism of Osteophytosis in Human Knee Osteoarthritisстатья

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