## 4 Discussion  
Bone remodeling is a process in which old or damaged bone is removed by osteoclasts and replaced with new bone formed by osteoblasts. Osteoblasts-mediated bone formation and osteoclast-mediated bone resorption balance dysregulation lead to abnormal bone remodeling, leading to osteoporosis [39]. Throughout life, bone tissue undergoes continuous remodeling that requires the concerted action of bone-forming osteoblasts and bone-resorbing osteoclasts [40]. The current research trend for anti-osteoporotic treatment and prevention is to induce bone remodeling through the regulation of osteoblasts or osteoclasts using natural dietary compounds. _B. hispida_ (Thunb.) Cogn. is a cucurbitaceae, a food material with potential for functional food production. _B. hispida_ fruit has pharmacological activities such as antioxidant, anti-inflammatory, gastoprotective, and neuroprotective properties [32; 34; 35; 36; 41]. The various pharmacological effects of _B. hispida_ can be attributed to the presence of phenolic compounds. Previous studies reported the identification of astilbin, catechin, and narningenin in _B. hispida_ fruit, and the quantification of gallic acid [28; 42]. Despite the several health benefits associated with _B. hispida_, studies investigating its therapeutic efficacy on bone health have not yet been conducted. In this study, the chemical components of _B. hispida_ extract (HR1901-W) were isolated and identified, and their ability to regulate factors related to the differentiation and proliferation of osteoblasts and osteoclasts was evaluated. We analyzed the chemical components of HR1901-W. The main chemical component of HR1901-W was identified as 2-furoic acid (0.37 \(\pm\) 0.01 mg/dry weight in g). 2-Furoic acid has been reported to be effective in reducing cholesterol and in controlling blood sugar level and osteoporosis [43; 44; 45]. The phytochemical constituents of _Celastrus paniculatus_ seed 70% ethanol extract included 1.61% 2-furoic acid [46], and the main sugar of _Castanea sativa Mill_ shells acetyl soluble extracts was 2-furoic acid (7.12%) [47]. Also, the content of 2-furoic acid in the aqueous extract of _Agave tequilana_ Weber leaves was reported to be 1.8-3.5 mg/L [48; 49]. Bone homeostasis is maintained by a balance between the synthesis of bone matrix by osteoblasts and resorption of the bone tissue by osteoclasts. We investigated the in vitro effects of HR1901-W on mouse osteoblast and osteoclast metabolism. The natural isoflavrup phytoestrogen genistein was used as a positive control. The natural decrease in endogenous estrogen synthesis during menopause in women increases the risk of osteoporosis due to a decrease in bone mineral density and negative changes in bone microarchitecture [50; 51]. Genistein has been shown to stimulate osteoblastic bone formation, inhibit osteoclastic bone resorption, and prevent bone loss in ovariectomized rats. In addition, the effect of decreasing bone resorption and increasing bone formation in postmenopausal women has been reported [52; 53; 54; 55; 56]. Osteoblasts secrete bone matrix proteins such as type I collagen, OCN, and ALP to produce proteins that constitute the bone [57; 58; 59]. Moreover, these factors are specific to early osteoblast differentiation, making them important factors that can determine the degree of differentiation of osteoblasts. They are expressed in high concentrations in the outer cell membrane of osteoblasts and mineralized tissues, and they are involved in the transport of inorganic phosphates during the mineralization process [60; 61; 62]. The osteoblast lineage is determined by the expression of Runx2 and \(\beta\)-catenin in multipotent mesenchymal stem cells. On the other hand, maturation of the committed osteoblast precursors is characterized by the activation and expression of ALP [63]. Mature osteoblasts are embedded in osteoids to form osteocytes, which are involved in the \(\beta\)-catenin-mediated synthesis of OCN and synthesis of the bone matrix to form bone mass.