Bone resorption diseases, including osteoporosis, are usually caused by excessive osteoclastogenesis. Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian serine/threonine kinase, may participate in the regulation of bone homeostasis and osteolytic metastasis. In this study, ULK1 expression during osteoclastogenesis was detected with RT-PCR. We knocked down or overexpressed ULK1 through siRNA or lentiviral transduction in bone marrow macrophage (BMM). TRAP and phalloidin staining were performed to detect the osteoclastogenesis activity. Ovariectomized (OVX) mouse model of osteoporosis and a mouse of model osteoclast-induced bone resorption were applied to explore the role of ULK1 in bone resorption in vivo. The results showed that ULK1 expression was downregulated during osteoclast differentiation and was clinically associated with osteoporosis. ULK1 inhibited osteoclast differentiation in vitro. Knockdown of ULK1 expression activated phosphorylation of c-Jun N-terminal kinase (JNK) and spleen tyrosine kinase (Syk). Docking protein 3 (DOK3) was coexpressed with ULK1 during osteoclastogenesis. Downregulation of DOK3 offsets the effect of ULK1 on osteoclastogenesis and induced phosphorylation of JNK and Syk. Activation of ULK1 impeded bone loss in OVX mice with osteoporosis. Additionally, upregulation of ULK1 inhibited osteoclast-induced bone resorption in vivo. Therefore, our study reveals a novel ULK1/DOK3/Syk axis that regulates osteoclast differentiation and bone resorption, and targeting ULK1 is a potential therapeutic strategy for osteoporosis.

罗道病(Rosai-Dorfman disease,RDD)又称窦组织细胞增生伴巨淋巴结病,是一种病因不明、系统多发的良性淋巴组织增生性疾病,可同时累及人体各系统器官,目前在心血管系统、神经系统、消化系统等均有报道.自1969年,由Rosai和Dorfman将其正式命名后[1],国内外罗道病相关个案报道达1 200余例,国内80余例.其中骨骼系统罗道病报道近200例,胫骨罗道病个案报道不足20例,现结合文献综述报道1例左侧胫骨罗道病.