Lumpy skin disease (LSD) is an acute and sub-acute viral infectious disease of cattle caused by lumpy skin disease virus (LSDV), a member of the genus Capripoxvirus (CaPV) and family Poxviridae (Babiuk et al., 2008b, Tuppurainen and Oura, 2012). LSD mainly affects cattle and has a tremendous economic impact on the world's livestock industry and animal husbandry economy (Abutarbush et al., 2015, Casal et al., 2018, Gari et al., 2011). The primary transmission route of LSDV is the bite of insects and tick vectors (Sanz-Bernardo et al., 2021). Meanwhile, LSDV can also spread through contact transmission to another from one animal (Mazloum et al., 2023). The clinical signs of LSD are characterized by fever, lymphadenopathy, skin edema, body weight loss, and typical lesions such as papules or skin nodules in the skin, mucosa, and viscera (Al-Salihi and Hassan, 2015, Tageldin et al., 2014).

LSD is becoming increasingly severe and epidemic worldwide due to the lack of timely vaccination and effective drug treatments. The first LSD outbreak was officially recorded in 1929 in Zambia, in Sub-Saharan Africa (Babiuk et al., 2008a, Woods, 1988). In the 21st century, the geographical spread of LSD has extended from Africa to the Middle East, Eastern Europe, and Asia (Babiuk et al., 2008a, Sprygin et al., 2018, Tuppurainen and Oura, 2012). LSDV is a rapidly emerging pathogen in China. The initial outbreaks of LSD were officially reported in Qapqal Xibe Autonomous County, Ili Kazakh Autonomous Prefecture, Xinjiang, northwestern China (Lu et al., 2021). Since then, several LSD epidemics have been formally reported in 14 provinces or municipalities, including Fujian, Jiangxi, Guangdong, Anhui, Zhejiang, Sichuan, Yunnan, Hong Kong, Shandong, and Inner Mongolia (Flannery et al., 2021, Lu et al., 2021, Ren et al., 2023).

Current prevention and control of LSD relies mainly on vaccination with live attenuated vaccine. Based on the antigenic homology and cross-protection between sheeppox virus (SPPV), goatpox virus (GTPV), and LSDV, the homologous live attenuated vaccine of SPPV and GTPV could be potentially applied for protection against LSDV (Tuppurainen and Oura, 2012). Two live attenuated strains of CaPV (LSDV Neethling strain and SPPV RM-65 strain) were specifically recommended and used as vaccines for the control and prevention of LSD (Brenner et al., 2009, Carn, 1993). Currently, only LSDV live attenuated vaccines have been demonstrated to be effective in the eradication of LSDV (European Food Safety et al., 2020). Still, the cross-protective efficiency of the homologous live attenuated SPPV and GTPV vaccine for LSDV infection must be re-evaluated (Brenner et al., 2009, Kara et al., 2018).

Viruses are obligate intracellular parasites that entirely rely on host cells to complete the replication life cycle and produce the progeny (Walsh and Mohr, 2011). Screening the suitable cell model for virus replication is vital for developing a vaccine and subsequent pathogenetic mechanism research (Kaiser et al., 2016, Manini et al., 2017, Suderman et al., 2021b). Previous studies have reported that the Madin-Darby Bovine Kidney (MDBK), Vero, primary sheep testis cells (Primary ST), ovine testis cell line (OA3.Ts), embryonic skin of sheep (Esh-l), fetal cow skin fibroblast cell line (hTERT-CSF), hTERT-Sheep testicle cell (hTERT-ST), and BHK-21 enable support the LSDV replication (Babiuk et al., 2007, Kaiser et al., 2016, Ma et al., 2023, Manini et al., 2017, Suderman et al., 2021a). Notable, BHK-21, which is isolated from the kidney of an uninfected golden hamster (Mesocricetus auratus), is a rodent-derived permissive cell line to LSDV infection (Macpherson and Stoker, 1962).

The murine osteoblastic cell line MC3T3-E1 has been established from the calvaria of a C57BL/6 mouse and selected based on high alkaline phosphatase activity in the resting state (Wang et al., 1999). The cell can differentiate into osteoblasts and osteocytes and has been shown to form calcified bone tissue in vitro, which is used as a cell model to study the molecular mechanisms involved in the differentiation and mineralization of osteoblasts (Wang et al., 1999). Our previous comparative study has identified that the murine-derived BHK-21 is a highly susceptible cell model to LSDV infection (Ren et al., 2022b). There is no doubt that the successful screening of the murine-derived cell model facilitated the pathogenesis research of LSDV. In this present, this murine-origin MC3T3-E1 is first identified as a suitable cell line for LSDV replication, providing a novel cell model for further research.