Fibroblast-like synoviocytes induce calcium mineral formation and deposition.

Yubo Sun,Edward N Hanley,Harry James Norton,David R Mauerhan,Natalia Zinchenko,Helen E Gruber,Atiya M Franklin

doi:10.1155/2014/812678

Yubo Sun, Edward N Hanley + Show 5 more

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https://doi.org/10.1155/2014/812678

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Journal: Arthritis	Publication Date: May 20, 2014
Citations: 59	License type: CC BY 3.0

Affiliation: Carolinas Medical Center

Abstract

Calcium crystals are present in the synovial fluid of 65%–100% patients with osteoarthritis (OA) and 20%–39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s). The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

Highlights

Basic calcium phosphate (BCP) crystals and calcium pyrophosphate dihydrate (CPPD) crystals are the two most common forms of articular crystals
We examined and compared the expression of genes implicated in the biomineral formation biological process in OA fibroblast-like synoviocytes (FLSs) and rheumatoid arthritis (RA) FLSs, FLSs-mediated calcium mineral formation and deposition in the absence and presence of ATP in regular medium, and chondrogenesis differentiating medium and osteogenesis differentiation medium to test the hypothesis that OA FLSs are not bystanders but potentially active players in the pathological calcification process occurring in OA
We recently reported that numerous genes implicated in the inflammatory response biological process are differentially expressed in hTERT-OA 13A FLSs and hTERT-RA 516 FLSs [21]

Summary

Introduction

Basic calcium phosphate (BCP) crystals and calcium pyrophosphate dihydrate (CPPD) crystals are the two most common forms of articular crystals. Find that these calcium crystals are associated with end-stage OA in all cases and that the extent of cartilage calcification correlates with the histological grade of cartilage degeneration and clinical symptoms [3,4,5,6]. Studies found that more calcium minerals are formed and deposited in the cultures of OA chondrocytes and meniscal cells than in the cultures of normal chondrocytes and meniscal cells [4, 6]. These findings indicate that pathological calcification is an active component of the OA disease process. It is believed that PC exerts its disease-modifying activity on OA, at least in part, by inhibiting the formation of articular calcium crystals [15]

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