Osteogenic differentiation of human lens epithelial cells might contribute to lens calcification

Abstract

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.

Klotho suppresses high phosphate-induced osteogenic responses in human aortic valve interstitial cells through inhibition of Sox9

“…It is likely that high Pi is responsible for the upregulation of Sox9 observed in this study. In this regard, high Pi has been reported to upregulate the expression of Sox9 in human endothelial cells and smooth muscle cells [26, 40]. The findings of the present study highlight a novel role of Sox9 in mediating the osteogenic responses of human AVICs to high Pi.…”

[Retracted] Iron‐Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta‐Catenin Signaling

“…An association between excess iron and osteoporosis as well as fracture has been shown which is attributed to the detrimental effect of iron on bone. Iron overload decreases osteoplastic activity and facilitates osteoplastic differentiation and bone resorption; furthermore, iron inhibits differentiation of bone marrow mesenchymal cells and bone remodeling, through induction of ferritin [21,22]. FAC, respectively.…”

Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation

“…Lens calcification occurs in senile cataracts and in young patients with congenital cataracts or chronic uveitis (Balogh et al 2016). Chronic uveitis is an inflammatory disease affecting the uvea, the middle layer of the eye (Figure 3).…”

“…In mammalian cells, excess Ca 2þ simulates more glucose oxidation and mitochondrial ATP production (Griffiths and Rutter 2009), perhaps promoting LEC proliferation, osteogenic differentiation of LECs and their subsequent migration (Balogh et al 2016). Epithelial and fibroblast cell-cell contact is dependent on extracellular Ca 2þ levels (Mukai et al 2006).…”