To assess the chronological participation of sclerostin and FGF23 in bone metabolism, this study tracked the immunolocalization of sclerostin and FGF23 in the metaphyses of murine long bones from embryonic day 18 (E18) through 1 day after birth, 1 week, 2 weeks, 4 weeks, 8 weeks, and 20 weeks of age. We have selected two regions in the metaphyseal trabeculae for assessing sclerostin and FGF23 localization: close to the chondro-osseous junction, i.e., bone modeling site even in the adult animals, and the trabecular region distant from the growth plate, where bone remodeling takes place. As a consequence, sclerostin-immunopositive osteocytes could not be observed in both close and distant trabecular regions early at the embryonic and young adult stages. However, osteocytes gradually started to express sclerostin in the distant region earlier than in the close region of the trabeculae. Immunoreactivity for FGF23 was observed mainly in osteoblasts in the early stages, but detectable in osteocytes in the later stages of growth in trabecular and cortical bones. Fgf23 was weakly expressed in the embryonic and neonatal stages, while the receptors, Fgfr1c and αKlotho were strongly expressed in femora. At the adult stages, Fgf23 expression became more intense while Fgfr1c and aKlotho were weakly expressed. These findings suggest that sclerostin is secreted by osteocytes in mature bone undergoing remodeling while FGF23 is synthesized by osteoblasts and osteocytes depending on the developmental/growth stage. In addition, it appears that FGF23 acts in an autocrine and paracrine fashion in fetal and neonatal bones.By establishing a communication network between osteocytes and osteoblasts, osteocytes are situated at the center of bone turnover and help determine how bones adjust to mechanical stress through bone remodeling. Osteocytes exist inside osteocytic lacunae and connect to neighboring osteocytes and osteoblasts on the bone surfaces via fine cytoplasmic processes that run through osteocytic canaliculi. Osteocytes interconnect their cytoplasmic processes via gap junctions (2,6,7,33), thereby building functional syncytia referred to as osteocytic lacunar-canalicular system (OLCS) (5,15,16,31). In the last few decades, many studies have reported on important osteocyte-derived factors, such as sclerostin (which regulates osteoblastic activities) and fibroblast growth factor 23 (FGF23, which affects the proximal renal tubules to reduce serum