Department of Pharmaceutical Sciences and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Division of Endocrinology, Department of Internal Medicine, Center for Musculoskeletal Disease Research and Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
J Biol Chem. 2023 Feb;299(2):102841. doi: 10.1016/j.jbc.2022.102841. Epub 2022 Dec 24.
Hem1 (hematopoietic protein 1), a hematopoietic cell-specific member of the Hem family of cytoplasmic adaptor proteins, is essential for lymphopoiesis and innate immunity as well as for the transition of hematopoiesis from the fetal liver to the bone marrow. However, the role of Hem1 in bone cell differentiation and bone remodeling is unknown. Here, we show that deletion of Hem1 resulted in a markedly increase in bone mass because of defective bone resorption in mice of both sexes. Hem1-deficient osteoclast progenitors were able to differentiate into osteoclasts, but the osteoclasts exhibited impaired osteoclast fusion and decreased bone-resorption activity, potentially because of decreased mitogen-activated protein kinase and tyrosine kinase c-Abl activity. Transplantation of bone marrow hematopoietic stem and progenitor cells from wildtype into Hem1 knockout mice increased bone resorption and normalized bone mass. These findings indicate that Hem1 plays a pivotal role in the maintenance of normal bone mass.
Hem1（造血蛋白 1）是 Hem 家族细胞质衔接蛋白的一个造血细胞特异性成员，对淋巴发生和先天免疫以及造血从胎儿肝脏向骨髓的过渡至关重要。然而，Hem1 在骨细胞分化和骨重塑中的作用尚不清楚。在这里，我们发现 Hem1 的缺失导致雌雄小鼠的骨量明显增加，这是由于骨吸收受损所致。Hem1 缺陷的破骨细胞前体细胞能够分化为破骨细胞，但破骨细胞融合受损，骨吸收活性降低，可能是由于丝裂原活化蛋白激酶和酪氨酸激酶 c-Abl 活性降低所致。将来自野生型小鼠的骨髓造血干细胞和祖细胞移植到 Hem1 敲除小鼠中，可增加骨吸收并使骨量正常化。这些发现表明，Hem1 在维持正常骨量方面发挥着关键作用。
