Abstract

Excerpt:

Results of previous studies have shown that fluoride has a higher and special affinity for calcium in bone tissue, which could result in osteofluorosis (19,20). It has been reported that osteofluorosis may increase the severity of osteoarthritis (OA) characterized by progressive degeneration of articular cartilage (21,22). Chondrocyte apoptosis may be involved in the onset and development of osteoarthritic cartilage degeneration (23). Previously, chondrocytes were found to be responsible for the synthesis of cartilage extracellular matrix (ECM) (24,25), while ECM is considered crucial to the survival of chondrocytes (26,27). Subsequently, there is a close correlation between chondrocyte apoptosis and the synthesis of ECM. Additionally, fluoride may induce OA by promoting chondrocytes apoptosis and disrupting the synthesis of ECM in cartilage; however, the molecular mechanism involved remains to be determined.

Hypoxia-inducible factor 1a (HIF-1a) is important in the maintenance of the survival of chondrocytes. HIF-1a may inhibit the apoptosis of chondrocytes and regulate the synthesis of ECM (28-30). This synthesis may be mediated by transactivation of sex determining region Y box gene 9 (Sox9), a key transcription factor for chondrocyte-specific genes such as collagen II (Col II) which encode the Col II protein (31,32). Thus, we hypothesized that sodium fluoride (NaF) would induce chondrocytes apoptosis through the downregulation of HIF-1a and cause matrix disruption through the downregulation of HIF-1a via the Sox9 pathway.

The purpose of this study was to demonstrate the molecular mechanism of NaF on apoptosis in primary cultured rat chondrocytes.

 

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