Kim, Soon-Young Park, Gun-Il Park, Seung-Yoon Lee, Eun-Hye Choi, Hyuck Koh, Jeong-Tae Han, Soyun Choi, Man Ho Park, Eui Kyun Kim, In-San Kim, Jung-Eun 2024-01-19T09:33:30Z 2024-01-19T09:33:30Z 2023-03-23 2023-05 0021-9541 https://pubs.kist.re.kr/handle/201004/113779 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 17 beta-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. English John Wiley & Sons Inc. Gulp1 deficiency augments bone mass in male mice by affecting osteoclasts due to elevated 17 beta-estradiol levels Article 10.1002/jcp.30987 1 Journal of Cellular Physiology, v.238, no.5, pp.1006 - 1019 Journal of Cellular Physiology 238 5 1006 1019 N scie scopus 000943598400001 2-s2.0-85149559667 Cell Biology Physiology Cell Biology Physiology Article ADAPTER PROTEIN GULP SEALING ZONE APOPTOTIC CELLS MINERAL DENSITY ASSOCIATION ENGULFMENT EXPRESSION ESTROGEN HORMONE ESTRADIOL 17 beta-estradiol adaptor protein deficiency Gulp1 osteoclast