BackgroundCardiotrophin-like cytokine factor 1 (CLCF1) is a member of the IL (interleukin)-6-type cytokine. Although its immunomodulatory functions are well defined, data on the physiological and pathological functions of the CLCF1 in bone metabolism remains scant. Here, we interrogated the functions and mechanisms of CLCF1 in osteoblast differentiation.MethodsA total of 109 patients with postmenopausal osteoporosis (PMOP) and 94 control group participants were included in this study. Quantitative reverse transcription PCR (RT-qPCR) and Western blot techniques were used to profile the expression of the CLCF1, nuclear factor-kB ligand and its decoy receptor osteoprotegerin (RANKL/OPG), as well as the janus activated kinase (JAK2)/transcription3 (STAT3) pathway. To elucidate the effect of CLCF1 on bone metabolism, we established CLCF1 gene-knockout Raji cell lines and Raji-MG-63 co-culture system, and interrogated the osteoblast differentiation by measuring the activity of ALP and the level of Alizarin-Red S staining.ResultsOur data demonstrated that the expression of CLCF1 was highly downregulated in PMOP compared with the control group. Moreover, the level of CLCF1 was proportional to the bone mineral density (BMD) in the postmenopausal osteoporosis. Furthermore, the deletion of CLCF1 gene inhibits osteoblast differentiation by regulating the RANKL/OPG system.ConclusionOur findings unravel the previously unidentified roles of CLCF1 in the bone-immune crosstalk, as well as potential therapeutic strategies for postmenopausal osteoporosis.