The DNA Repair Enzyme Apurinic/Apyrimidinic Endonuclease (Apex Nuclease) 2 Has the Potential to Protect against Down-Regulation of Chondrocyte Activity in Osteoarthritis

Abstract

Apurinic/apyrimidinic endonuclease 2 (Apex 2) plays a critical role in DNA repair caused by oxidative damage in a variety of human somatic cells. We speculated that chondrocyte Apex 2 may protect against the catabolic process of articular cartilage in osteoarthritis (OA). Higher levels of Apex 2 expression were histologically observed in severely compared with mildly degenerated OA cartilage from STR/OrtCrlj mice, an experimental model which spontaneously develops OA. The immunopositivity of Apex 2 was significantly correlated with the degree of cartilage degeneration. Moreover, the OA-related catabolic factor interleukin-1β induced the expression of Apex 2 in chondrocytes, while Apex 2 silencing using small interfering RNA reduced chondrocyte activity in vitro. The expression of Apex 2 in chondrocytes therefore appears to be associated with the degeneration of articular cartilage and could be induced by an OA-related catabolic factor to protect against the catabolic process of articular cartilage. Our findings suggest that Apex 2 may have the potential to prevent the catabolic stress-mediated down-regulation of chondrocyte activity in OA.

Mechanical and oxidative stress in osteoarthritis

“…We observed that APEX2 expression in chondrocytes was induced by OA-related catabolic factors in vitro, and was associated with the degeneration of articular cartilage in an in vivo OA mouse model (Fig. 5) 35) .…”

“…Furthermore, downregulation of APEX2 using small interfering RNA decreased chondrocyte activity in vitro 35) . These findings indicate that APEX2 may prevent the oxidative stress-induced downregulation of chondrocyte activity in OA.…”

“…Oxidative DNA lesions accumulate in nuclear and mitochondrial genomes during aging, and this can increase dramatically in age-related neurodegenerative diseases such as Parkinson's disease [32][33][34] . Regarding musculoskeletal diseases, we previously reported that oxidative DNA damage in chondrocytes accumulates in the degenerated articular cartilage in OA, reducing its maintenance potential 35) .…”

<p>A novel, self-assembled artificial cartilage&ndash;hydroxyapatite conjugate for combined articular cartilage and subchondral bone repair: histopathological analysis of cartilage tissue engineering in rat knee joints</p>

“…Previously, we observed that the HA-AG/type II collagen self-organized complex consisted of 10-500 µm long (2-50 nm diameter) collagen fibers at pH 6-10. 2,34 HA retains AG molecule in the matrix through specific protein-HA interactions. It is thought that HA forms a scaffold for binding large chondroitin sulfate proteoglycans (AG) in the articular cartilage tissue.…”

“…The sections were stained with H&E for histological assessment of the general morphology of the repair tissue, or Safranin O/fast green (SO/FG) and toluidine blue, to indicate glycosaminoglycan content as per standard protocols. 34…”