**3.5 Gelsolin (GSN)**

Gelsolin is a calcium-dependent actin-binding protein that cleaves, caps, and nucleates actin to regulate cytoskeleton structure, cell movement and metabolic processes, and also participates in regulation of cell signal transduction and apoptosis [89]. As an actin-binding protein involved in the assembly and movement of osteoclast cell feet. GSN deficiency can hinder the assembly of osteoclast cell feet and increase bone mass and bone strength. Furthermore, GSN can hinder the assembly of osteoclasts to the bone matrix through integrins activation, thereby ultimately activating osteoclasts and promoting bone resorption [90]. Therefore, in different clinical studies, the relationship between GSN and BMD is not consistent. A Mexican study found that serum GSN levels were reduced in postmenopausal women with low bone mass and osteoporosis but the difference between groups was not statistically significant [90]. Peripheral blood mononuclear cells (PBMs), as precursors of osteoclasts, produce cytokines important for osteoclast development and play an important role in bone metabolism. A cytoplasmic proteomic analysis of PBMs from Caucasian men with very high and very low BMD found that GSN expression was significantly increased in patients with very low BMD [91]. The same study of more than 6000 subjects with very high and very low bone density samples found that there was no significant difference in plasma GSN between men with very high and very low bone density, but GSN levels in postmenopausal women were higher than the extremely low BMD group, and it was negatively correlated with hip BMD [92]. Deng et al. (2014) also found that GSN protein and mRNA levels in the PBM of subjects with low BMD were down-regulated, and SNP rs767770 was only significantly correlated with hip BMD in female Caucasians, suggesting that GSN is an important gene affecting hip BMD in female Caucasians [93]. A study on the correlation between GSN and BMD in Chinese postmenopausal women found that the GSN level in postmenopausal women was significantly higher than that in premenopausal women, and compared with the normal BMD group, the plasma GSN level in the low bone mass or osteoporosis group was significantly higher. There is a negative correlation between plasma GSN and hip BMD in postmenopausal women, and GSN is an independent influencing factor of femoral neck and lumbar spine BMD [94]. In conclusion, the current research shows that plasma GSN may be used as a biochemical marker of bone resorption for the diagnosis of osteoporosis, but more in-depth and extensive research is still needed.
