Osteogenic differentiation of human lens epithelial cells might contribute to lens calcification.
Calcification of the human lens has been described in senile cataracts and in young patients with congenital cataract or chronic uveitis. Lens calcification is also a major complication of cataract surgery and plays a role in the opacification of intraocular lenses. A cell-mediated process has been suggested in the background of lens calcification, but so far the exact mechanism remained unexplored. Lens calcification shares remarkable similarities with vascular calcification; in both pathological processes hydroxyapatite accumulates in the soft tissue. Vascular calcification is a regulated, cell-mediated process in which vascular cells undergo osteogenic differentiation. Our objective was to investigate whether human lens epithelial cells (HuLECs) can undergo osteogenic transition in vitro, and whether this process contributes to lens calcification. We used inorganic phosphate (Pi) and Ca to stimulate osteogenic differentiation of HuLECs. Osteogenic stimuli (2.5mmol/L Pi and 1.2mmol/L Ca) induced extracellular matrix mineralization and Ca deposition in HuLECs with the critical involvement of active Pi uptake. Osteogenic stimuli almost doubled mRNA expressions of osteo-/chondrogenic transcription factors Runx2 and Sox9, which was accompanied by a 1.9-fold increase in Runx2 and a 5.5-fold increase in Sox9 protein expressions. Osteogenic stimuli induced mRNA and protein expressions of alkaline phosphatase and osteocalcin in HuLEC. Ca content was higher in human cataractous lenses, compared to non-cataractous controls (n=10). Osteocalcin, an osteoblast-specific protein, was expressed in 2 out of 10 cataractous lenses. We conclude that osteogenic stimuli induce osteogenic differentiation of HuLECs and propose that this mechanism might play a role in lens calcification.
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Enikő
E
Balogh
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Andrea
A
Tóth
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Emese
E
Tolnai
Department of Neurology, Bethesda Children's Hospital, Budapest, Hungary.
Tímea
T
Bodó
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Emese
E
Bányai
Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Dóra Júlia
DJ
Szabó
Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary; Center of Eye Research, Department of Ophthalmology, Oslo University Hospital and University of Oslo, Oslo, Norway.
Goran
G
Petrovski
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: jeneyv@belklinika.com.
Viktória
V
Jeney
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002114:Calcinosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002386:Cataract / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D010710:Phosphates / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D050659:Core Binding Factor Alpha 1 Subunit; D010710:Phosphates; C493709:RUNX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D002118:Calcium
Aging disease; Calcification; Cataract; Human lens epithelial cells; Osteogenic differentiation