Crocin attenuates methylglyoxal-induced osteoclast dysfunction by regulating glyoxalase, oxidative stress, and mitochondrial function

Methylglyoxal (MG), a highly reactive dicarbonyl compound, is a major cell-permeant precursor of advanced glycation end-products, which are associated with several conditions, including diabetes and degenerative diseases. Crocin, a constituent of saffron, is involved in many pharmacological activities. Recent studies have reported that crocin exerts protective effects against bone diseases. Osteoclasts are multinucleated cells derived from hematopoietic stem cells that are responsible for bone resorption. The up- or down-regulation of their proliferation and differentiation is often associated with many bone-related diseases. The present study aimed to investigate the effects of crocin on osteoclast differentiation and to clarify its mechanism of action in the presence of MG. We demonstrated that crocin reversed MG-induced inhibition of tartrate-resistant acid phosphatase activity and bone resorption activity in osteoclasts. Quantitative reverse transcription-polymerase chain reaction analysis indicated that crocin treatment decreased the expression of TNF receptor-associated factor-6 (TRAF6), Akt2, extracellular-signal-regulated kinase-1 (ERK1), osteopetrosis-associated transmembrane protein 1 (OSTM1), and matrix metalloproteinase 9 (MMP-9) genes in the presence of MG. Crocin pretreatment also reversed MG-induced changes in mitochondrial mass, mitochondrial membrane potential, mitochondrial superoxide, and glyoxalase I levels. Taken together, our data suggest that crocin may be a useful therapeutic agent for the treatment of diabetic bone disorders.