THOC5 regulates human osteoclastogenesis

• Published in: European journal of cell biology 2022-06, Vol.101 (3), p.151248-151248, Article 151248
• Main Authors: Mun, Se Hwan, Oh, Brian, Lee, Min Joon, Bae, Seyeon, Yang, Young, Park-Min, Kyung-Hyun
• Format: Article
• Language: English
• Subjects: Bone Resorption; C-FMS; Cell Differentiation; Humans; M-CSF; Macrophage Colony-Stimulating Factor - metabolism; Macrophage Colony-Stimulating Factor - pharmacology; Nuclear Proteins - metabolism; Osteoclasts; Osteoclasts - metabolism; Osteogenesis; THOC5
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2022.151248

Osteoclasts are bone resorbing cells that are responsible for physiological and pathological bone resorption. Macrophage colony stimulating factor (M-CSF) binds to the M-CSF receptor (c-FMS) and plays a key role in the differentiation and survival of macrophages and osteoclasts. THOC5, a member of the THO complex, has been shown to regulate hematopoiesis and M-CSF-induced macrophage differentiation. However, the role of THOC5 in osteoclasts remains unclear. Here, our study reveals a new role of THOC5 in osteoclast formation. We found that THOC5 shuttles between nucleus and cytoplasm in an M-CSF signaling dependent manner. THOC5 bound to FICD, a proteolytic cleavage product of c-FMS, and THOC5 facilitates the nuclear translocations of FICD. Decreased expression of THOC5 by siRNA-mediated knock down suppressed osteoclast differentiation, in part, by regulating RANK, a key receptor of osteoclasts. Mechanistically, knock down of THOC5 inhibited the expression of RANKL-induced FOS and NFATc1. Our findings highlight THOC5′s function as a positive regulator of osteoclasts. •THOC5 positively regulates human osteoclastogenesis.•The subcellular localizations of THOC5 were dynamically regulated by c-FMS signaling in human macrophages.•THOC5 binds to c-FMS intracellular domains (FICDs) and the THOC5/FICD complex translocates into the nucleus.•THOC5 modulates RANK expression in an M-CSF dependent manner.