Regulation of osteoblast and osteoclast functions by FGF‐6

Abstract

Fibroblast growth factor-6 (FGF-6) is known to be the key ligand for fibroblast growth factor receptor 4 (FGFR4) during muscle regeneration but its role in bone has yet to be verified. FGFR signaling is known to be important in the initiation and regulation of osteogenesis, so in this study the actions of FGF-6 on human osteoblasts and osteoclasts were investigated. Human primary osteoblasts (hOB) were used to study the effect of FGF-6 on proliferation (by ATP quantification), signal transduction (by ERK and AKT phosphorylation), differentiation (by alkaline phosphatase activity, APA), and mineralization (by calcein staining). To study FGF-6 activity on osteoclast differentiation, human bone marrow cells were used and tartrate-resistant acid phosphatase (TRAP) multinucleated cells together with actin filaments arrangements were quantified. Human primary mature osteoclasts were used to evaluate the effect of FGF-6 on osteoclast reabsorbing activity by reabsorbed pit measurements. FGF-6 >10(-9) M as FGF-2 10(-7) M induced hOB proliferation mediated by pERK together with a reduction in APA and reduced mineralization of the treated cells. Moreover FGF-6 increased the formation of TRAP-positive multinucleated cells in a dose-dependent manner (maximal effect at 10(-8) M). FGF-6-treated cells showed also a greater percentage of cells that formed typical osteoclast sealing zones. Mature osteoclasts cultured on dentine slice increased the area of reabsorption with a maximal effect of FGF-6 at 10(-12) M. FGF-6 may be considered a regulator of bone metabolism as shown by its activity on both osteoblasts and osteoclasts.

Fibroblast growth factor signaling in skeletal development and disease

“…FGF18 can also induce osteoclast formation and function indirectly through stimulating receptor activator of the nuclear factor-κB ligand (RANKL) and cyclooxygenase-2 expression in osteoblasts (Shimoaka et al 2002). Another study showed that FGF6 increased the formation and resorbing activity of human primary mature osteoclasts in vitro (Bosetti et al 2010), whereas FGF8a inhibited osteoclastogenesis, but not osteoclast function, in mouse bone marrow cultures.…”

Gene-set based genome-wide association analysis for the speed of sound in two skeletal sites of Korean women

“…Mutations in P2RX7 gene have been associated with low lumbar spine BMD, and accelerated bone loss in post-menopausal women (18). FGFR signaling is known to be important in the initiation and regulation of osteogenesis, and the IIIc alternative of Fgfr2 is a positive regulator of bone formation, affecting mainly the osteoblast (19, 20). SYK(-/-) progenitors are similarly defective in osteoclast development and bone resorption (21).…”

Effects of 6‐Hydroxyflavone on Osteoblast Differentiation in MC3T3‐E1 Cells

“…Bone calcein labeling has been used earlier to assess the histomorphometry of remolded bones in vivo [42]. Calcein staining has also recently been introduced to examine and quantify osteoblast differentiation and the matrix mineralization of human primary osteoblasts [43]. Further, Calcein, also known as fluorexon or fluorescein complex, is a fluorescent dye with excitation and emission wavelength of 495/515 nm, respectively.…”