## 1 Introduction  
Orthodontic tooth movement (OTM) can be achieved by the remodeling process of periodontal tissue, including cement and alveolar bone. When orthodontic force is applied, the pressure induces osteocl mineralized tissue degradation on the compression side and mineralization by osteoblasts on the tension side [1]. This mineralized tissue turnover is the coupling mechanism of bone resorption followed by bone formation and is known as a marker that influences OTM [2]. Alveolar bone remodeling is influenced by localized tooth-related factors [3]. Systemic factors such as menopause [4], aging [5], osteoporosis [6], changes in parathyroid hormone levels [7], and levels of steroid [8] or bisphosphonate intake can also influence the overall alveolar bone turnover rate [9]. It is well known that reduced alveolar bone turnover rates can impede the overall velocity of tooth movement during orthodontic treatment [10]. Certain levels of tooth root resorption are an unavoidable consequence caused by orthodontic forces, and there have been many efforts to minimize it [11; 12; 13; 14]. Unfortunately, severe resorption, defined as a reduction that is more than 4 mm or a third of the original length of the root, occurs in 1% to 5% of treated teeth [11]. The etiology of root resorption is multifactorial; there are patient-related factors such as genetic predisposition [12], treatment-related factors including extensive treatment duration or tooth movement [13], and local factors of the tooth itself [14]. However, none of these factors have been clearly proven as the principal cause of root resorption [11]. Bone metabolism not only affects the acceleration of tooth movement but also modifies the periodontal tissue and therefore the extent of root resorption [15]. A low bone turnover rate is considered to be a predisposing factor for root resorption, and high bone turnover is associated with less root resorption [16]. Moreover, studies have shown that periodic vibration [17] and low-level laser therapy (LLLT) stimulation during orthodontic treatment can increase the rate of bone turnover and thus reduce the extent of root resorption [18]. In the case of an ovariectomized mouse model, a lack of estrogen induces the imbalance of the receptor activator of the NF-kB ligand ( RANKL)/osteoprotegerin (OPG) system and increases root resorption during OTM [19]. The application of resveratrol in the rat model decreases root resorption during OTM but reduces the amount of OTM [20]. The agent for reducing root resorption during OTM should not inhibit OTM. However, this type of agent is rare. 4-hexylresorcinol (4 HR), a phenol derivative with anti-septic and anti-parasitic properties, has been used as a food preservative and as a means to prevent melanosis [21]. It is known to be safe and effective in topical applications for infected skin or mucosa [21]. 4 HR suppresses tumor necrosis factor-\(\alpha\)[22] and the nuclear factor-kB (NF-kB) signaling pathway [23] related to osteoclast differentiation, which increases bone formation by suppressing osteoclast activity and promoting angiogenesis [24]. 4 HR has been incorporated into bone-graft material and has been proven to prevent the formation of foreign-body giant cells [25] and suppress the NF-kB signaling pathway in osteoblasts [26]. Furthermore, it is known to activate transforming growth factor-\(\beta\)1 (TGF-\(\beta\)1) signaling, which induces bone regeneration and remodeling [27]. TGF-\(\beta\)1 activated by 4 HR induces angiogenesis independently of hypoxia inducible factor (HIF) [24; 28]. In tooth-related research, 4 HR increases bone turnover markers in blood samples and accelerates OTM [29]. The administration of 4 HR increases mineral deposition during tooth formation and mandibular incisor eruption in rat models [30]. Both bone turnover and mineral deposition during tooth formation are important for preventing root resorption during OTM. However, not much is known about its effects on root resorption during OTM.