Gulp1 deficiency augments bone mass in male mice by affecting osteoclasts due to elevated 17ß-estradiol levels.

The engulfment adaptor phosphotyrosine-binding domain containing 1 (GULP1) is an adaptor protein involved in the engulfment of apoptotic cells via phagocytosis. Gulp1 was first found to promote the phagocytosis of apoptotic cells by macrophages, and its role in various tissues, including neurons and ovaries, has been well studied. However, the expression and function of GULP1 in bone tissue are poorly understood. Consequently, to determine whether GULP1 plays a role in the regulation of bone remodeling in vitro and in vivo, we generated Gulp1 knockout (KO) mice. Gulp1 was expressed in bone tissue, mainly in osteoblasts, while its expression is very low in osteoclasts. Microcomputed tomography and histomorphometry analysis in 8-week-old male Gulp1 KO mice revealed a high bone mass in comparison with male wild-type (WT) mice. This was a result of decreased osteoclast differentiation and function in vivo and in vitro as confirmed by a reduced actin ring and microtubule formation in osteoclasts. Gas chromatography-mass spectrometry analysis further showed that both 17ß-estradiol (E2) and 2-hydroxyestradiol levels, and the E2/testosterone metabolic ratio, reflecting aromatase activity, were also higher in the bone marrow of male Gulp1 KO mice than in male WT mice. Consistent with mass spectrometry analysis, aromatase enzymatic activity was significantly higher in the bone marrow of male Gulp1 KO mice. Altogether, our results suggest that GULP1 deficiency decreases the differentiation and function of osteoclasts themselves and increases sex steroid hormone-mediated inhibition of osteoclast differentiation and function, rather than affecting osteoblasts, resulting in a high bone mass in male mice. To the best of our knowledge, this is the first study to explore the direct and indirect roles of GULP1 in bone remodeling, providing new insights into its regulation.

The association between blood cadmium level, frequency and amount of gejang (marinated crab) intake.

BACKGROUND: Gejang (marinated crab) is a favorite traditional food and a main source of crab intake among Koreans. The present study aimed to identify the possibility of cadmium inflow to the body through gejang; accordingly, the relationship between gejang intake frequency and amount, and blood cadmium concentrations was investigated. METHODS: Using data from the first Korea National Health and Nutrition Examination Survey in the sixth period in 2013, means and standard errors of blood cadmium concentrations in relation to gejang intake frequency and amount, as well as the monthly intake of gejang, were obtained from 1381 participants for whom data regarding blood cadmium concentration measurements was available. RESULTS: After adjustment for confounding factors, a gejang intake frequency of four or fewer times per week and a monthly intake of 200 cm(3) or less had no significant effect on blood cadmium concentrations. However, participants with gejang intake of at least five times per week had a weighted mean cadmium concentration of 2.12 µg/L (p < 0.001), and participants who had a gejang monthly intake of more than 200 cm(3) had a weighted mean cadmium concentration of 1.76 µg/L (p < 0.001). CONCLUSION: These results suggest that to minimize the effect of gejang consumption on blood cadmium level, gejang intake should be limited to four or less times per week and 200 cm(3) or less per month. Weekly intake of at least five times and monthly intake of more than 200 cm(3) may increase blood cadmium levels.