Anti-Müllerian Hormone Negatively Regulates Osteoclast Differentiation by Suppressing the Receptor Activator of Nuclear Factor-κB Ligand Pathway

Background@#Multiple members of the transforming growth factor-β (TGF-β) superfamily have well-established roles in bone homeostasis. Anti-Müllerian hormone (AMH) is a member of TGF-β superfamily of glycoproteins that is responsible for the regression of fetal Müllerian ducts and the transcription inhibition of gonadal steroidogenic enzymes. However, the involvement of AMH in bone remodeling is unknown. Therefore, we investigated whether AMH has an effect on bone cells as other TGF-β superfamily members do. @*Methods@#To identify the roles of AMH in bone cells, we administered AMH during osteoblast and osteoclast differentiation, cultured the cells, and then stained the cultured cells with Alizarin red and tartrate-resistant acid phosphatase, respectively. We analyzed the expression of osteoblast- or osteoclast-related genes using real-time polymerase chain reaction and western blot. @*Results@#AMH does not affect bone morphogenetic protein 2-mediated osteoblast differentiation but inhibits receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation. The inhibitory effect of AMH on osteoclast differentiation is mediated by IκB-NF-κB signaling. @*Conclusions@#AMH negatively regulates osteoclast differentiation without affecting osteoblast differentiation.

Anti-Müllerian Hormone Negatively Regulates Osteoclast Differentiation by Suppressing the Receptor Activator of Nuclear Factor-κB Ligand Pathway

Background@#Multiple members of the transforming growth factor-β (TGF-β) superfamily have well-established roles in bone homeostasis. Anti-Müllerian hormone (AMH) is a member of TGF-β superfamily of glycoproteins that is responsible for the regression of fetal Müllerian ducts and the transcription inhibition of gonadal steroidogenic enzymes. However, the involvement of AMH in bone remodeling is unknown. Therefore, we investigated whether AMH has an effect on bone cells as other TGF-β superfamily members do. @*Methods@#To identify the roles of AMH in bone cells, we administered AMH during osteoblast and osteoclast differentiation, cultured the cells, and then stained the cultured cells with Alizarin red and tartrate-resistant acid phosphatase, respectively. We analyzed the expression of osteoblast- or osteoclast-related genes using real-time polymerase chain reaction and western blot. @*Results@#AMH does not affect bone morphogenetic protein 2-mediated osteoblast differentiation but inhibits receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation. The inhibitory effect of AMH on osteoclast differentiation is mediated by IκB-NF-κB signaling. @*Conclusions@#AMH negatively regulates osteoclast differentiation without affecting osteoblast differentiation.

Bone Cell Communication Factors Provide a New Therapeutic Strategy for Osteoporosis / 전남의대학술지

Bone homeostasis is strictly regulated by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Many studies have shown that osteoclasts affect osteoblasts, and vice versa, through diffusible paracrine factors, cell-cell contact, and cell-bone matrix interactions to achieve the correct balance between osteoclastic and osteoblastic activities in the basic multicellular unit (BMU). The strict regulation that occurs during bone remodeling hinders the long-term use of the currently available antiresorptive agents and anabolic agents for the treatment of osteoporosis. To overcome these limitations, it is necessary to develop novel agents that simultaneously inhibit bone resorption, promote bone formation, and decouple resorption from formation. Therefore, a more detailed understanding of the mechanisms involved in osteoclast-osteoblast communication during bone remodeling is necessary.

Signaling Pathways in Osteoclast Differentiation / 전남의대학술지

Osteoclasts are multinucleated cells of hematopoietic origin that are responsible for the degradation of old bone matrix. Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-kappaB ligand (RANKL). M-CSF and RANKL bind to their respective receptors c-Fms and RANK to stimulate osteoclast differentiation through regulation of delicate signaling systems. Here, we summarize the critical or essential signaling pathways for osteoclast differentiation including M-CSF-c-Fms signaling, RANKL-RANK signaling, and costimulatory signaling for RANK.

Signaling Pathways in Osteoclast Differentiation / 전남의대학술지

Osteoclasts are multinucleated cells of hematopoietic origin that are responsible for the degradation of old bone matrix. Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-kappaB ligand (RANKL). M-CSF and RANKL bind to their respective receptors c-Fms and RANK to stimulate osteoclast differentiation through regulation of delicate signaling systems. Here, we summarize the critical or essential signaling pathways for osteoclast differentiation including M-CSF-c-Fms signaling, RANKL-RANK signaling, and costimulatory signaling for RANK.

Pro-inflammatory Cytokines Modulating Osteoclast Differentiation and Function

In general, bone homeostasis is maintained through the balance between bone formation and resorption. Disruption in this balance results in bone-related diseases such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Often, enhanced osteoclastogenesis is followed by accelerated bone resorption that is induced by pro-inflammatory cytokines in osteoporosis or rheumatoid arthritis, and leads to bone destruction. In this review study, factors involved in osteoclast differentiation and function are discussed, and how the prevention of such factors is effective in ameliorating bone loss in osteoporosis or rheumatoid arthritis.

Regulation of NFATc1 in Osteoclast Differentiation

Osteoclasts are unique cells that degrade the bone matrix. These large multinucleated cells differentiate from the monocyte/macrophage lineage upon stimulation by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL). Activation of transcription factors such as microphthalmia transcription factor (MITF), c-Fos, NF-kappaB, and nuclear factor-activated T cells c1 (NFATc1) is required for sufficient osteoclast differentiation. In particular, NFATc1 plays the role of a master transcription regulator of osteoclast differentiation. To date, several mechanisms, including transcription, methylation, ubiquitination, acetylation, and non-coding RNAs, have been shown to regulate expression and activation of NFATc1. In this review, we have summarized the various mechanisms that control NFATc1 regulation during osteoclast differentiation.

Identification of Alternatively Spliced Forms of human OSCAR in Osteoclasts

OBJECTIVES: Osteoclasts are multinucleated giant cells which can resorb bone and differentiated from hematopoietic cells. We have previously reported murine osteoclast-associated receptor (OSCAR) may be an important bone-specific regulator of osteoclast differentiation. We have cloned soluble form of human OSCAR (hOSCAR) and examined the role of hOSCAR on osteoclast differentiation. METHODS: Osteoclast differentiation was induced by treatment with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP) staining and pit formation were performed. Expression was measured by flow cytometry analysis, Northern and Western blot analysis. RESULTS: hOSCAR is expressed in osteoclast cells and involved in the differentiation of osteoclasts from peripheral blood mononuclear cells (PBMC). Two alternatively spliced forms (soluble hOSCAR [hOSCAR-S]) of hOSCAR were identified from osteoclasts complementary deoxyribonucleic acid (cDNA) library derived from PBMC. Putative transmembrane domain was not found in hOSCAR-S forms and it suggested that these forms might be secreted from osteoclast cells. These secreted forms of hOSCAR attenuated RANKL-induced osteoclast formation and bone resorption. CONCLUSIONS: Human osteoclasts express at least five different OSCAR messenger ribonucleic acid (mRNA) isoforms which could play different regulatory roles for differentiation. The secreted forms of hOSCAR might be a negative regulator of membrane-bounded forms of OSCAR.

Identification of Alternatively Spliced Forms of human OSCAR in Osteoclasts

OBJECTIVES: Osteoclasts are multinucleated giant cells which can resorb bone and differentiated from hematopoietic cells. We have previously reported murine osteoclast-associated receptor (OSCAR) may be an important bone-specific regulator of osteoclast differentiation. We have cloned soluble form of human OSCAR (hOSCAR) and examined the role of hOSCAR on osteoclast differentiation. METHODS: Osteoclast differentiation was induced by treatment with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP) staining and pit formation were performed. Expression was measured by flow cytometry analysis, Northern and Western blot analysis. RESULTS: hOSCAR is expressed in osteoclast cells and involved in the differentiation of osteoclasts from peripheral blood mononuclear cells (PBMC). Two alternatively spliced forms (soluble hOSCAR [hOSCAR-S]) of hOSCAR were identified from osteoclasts complementary deoxyribonucleic acid (cDNA) library derived from PBMC. Putative transmembrane domain was not found in hOSCAR-S forms and it suggested that these forms might be secreted from osteoclast cells. These secreted forms of hOSCAR attenuated RANKL-induced osteoclast formation and bone resorption. CONCLUSIONS: Human osteoclasts express at least five different OSCAR messenger ribonucleic acid (mRNA) isoforms which could play different regulatory roles for differentiation. The secreted forms of hOSCAR might be a negative regulator of membrane-bounded forms of OSCAR.

Osteoporosis and Vascular Calcification: Lesson from OPG KO Mice / 대한내분비학회지

No Abstract available.