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Abnormal collagen type 1 production in subchondral osteoarthritic osteoblasts is responsible in part for altered mineralization in these cells
Arthritis Research & Therapyvolume 9, Article number: P35 (2007)
Osteoarthritis (OA) is characterized by cartilage damage and loss, synovial membrane inflammation, and bone sclerosis and the formation of osteophytes. Bone sclerosis in OA is due to an abundant osteoid matrix that does not mineralize normally. The mechanism(s) responsible for this abnormal mineralization remain unknown. Here, we studied the link between the mineralization profile of normal and OA osteoblasts (Ob) in primary culture and the mechanisms responsible for this abnormal sclerosis.
Materials and methods
We prepared normal and OA Ob from subchondral bone of tibial plateaus. The expression of collagen type 1 α1 chains (COLL1A1) and α2 chains (COLL1A2) was determined by real-time PCR. In vitro mineralization was evaluated by alizarin red staining. We also determined the mineralization of human SaOS-2 cells, either transfected with the COLL1A1 cDNA or with siRNA for α1 chains. Conditioned-media (CM) fromOA Ob was used to alter the mineralization of SaOS-2 cells while SaOS-2 CM was used to determine whether this could correct OA Ob mineralization.
In vitro mineralization was reduced in OA Ob compared with normal Ob under basal conditions and following BMP-2 stimulation. This reduced mineralization was accompanied with an increase in COLL1A1 expression in OA Ob compared with normal, with no significant changes in COLL1A2, leading to an elevated COLL1A1 to COLL1A2 ratio in OA Ob. To determine the link between this ratio and mineralization, we used the SaOS-2 cell model. The COLL1A1 to COLL1A2 ratio in SaOS-2 cells varied from 7.5 to 1.5 from day 1 to day 14 postconfluence whereas mineralization progressively increased. Overexpressing COLL1A1 in SaOS-2 cells reduced whereas α1 chains siRNA transiently increased mineralization. In addition, SaOS-2 CM increased OA Ob mineralization while OA Ob CM reduced mineralization of SaOS-2 cells without any significant changes in the COLL1A1 to COLL1A2 ratio.
This study suggests that abnormal mineralization of OA bone tissue observed in vivo may be linked with an abnormal expression of COLL1A1 and with the release of a putative soluble factor by OA Ob. Production of an abnormal collagen matrix and a soluble factor by OA Ob leads to an abnormal osteoid matrix not mineralizing normally.