Reciprocal Gene Expression of Osteoclastogenesis Inhibitory Factor and Osteoclast Differentiation Factor Regulates Osteoclast Formation

Nagai, Masazumi; Sato, Nobuko

doi:10.1006/bbrc.1999.0524

Cited by 103 publications

(68 citation statements)

References 21 publications

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“…In the present study, however, a significant increase in the RANKL/OPG ratio was elicited by 1,25-(OH) 2 D 3 treatment at all time-points, including the most mature cultures. The up-regulation of RANKL by 1,25-(OH) 2 D 3 treatment was consistent with the known osteoclastogenic action of 1,25-(OH) 2 D 3 and agrees with a number of recent reports in cell line and immature primary cells (Horwood et al 1998, Yasuda et al 1998b, Nagai & Sato 1999. OPG was not significantly altered by 1,25-(OH) 2 D 3 , contrasting with its downregulation reported in previous studies in immature osteoblastic cells (Horwood et al 1998.…”

Section: Discussionsupporting

confidence: 91%

“…On the basis of these studies, it was previously suggested that regulation of RANKL and OPG by osteotropic agents such as 1,25-(OH) 2 D 3 did not occur or was significantly reduced in more mature osteoblastic cell lines (Horwood et al 1998, Nagai & Sato 1999. In the present study, however, a significant increase in the RANKL/OPG ratio was elicited by 1,25-(OH) 2 D 3 treatment at all time-points, including the most mature cultures.…”

Section: Discussioncontrasting

confidence: 46%

“…The importance of this pathway has been demonstrated in OPG knockout mice, which exhibit severe osteoporosis (Bucay et al 1998, Mizuno et al 1998, and transgenic mice overexpressing OPG, which have osteopetrosis (Simonet et al 1997). On the basis of these and other studies, it has been suggested that the ratio between RANKL and OPG expression levels in osteoblastic cells is a key factor in osteoclast regulation (Horwood et al 1998, Nagai & Sato 1999.…”

Section: Introductionmentioning

confidence: 99%

“…Previous in vitro studies of OPG/RANK/RANKL regulation have utilised stromal cells, immature primary osteoblasts and osteoblast cell lines (Horwood et al 1998, Hofbauer et al 1999, Lee & Lorenzo 1999, Nagai & Sato 1999, Shirai et al 1999, Suda et al 1999, Yasuda et al 1999. Immature osteoblasts and stromal cells enhance osteoclast recruitment and differentiation (Martin & Ng 1994).…”

Section: Introductionmentioning

confidence: 99%

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Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts

Thomas

Baker

Eisman³

et al. 2001

Journal of Endocrinology

165

114

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Osteoblast-osteoclast coordination is critical in the maintenance of skeletal integrity. The modulation of osteoclastogenesis by immature cells of the osteoblastic lineage is mediated through receptor activator of NF B (RANK), its ligand RANKL, and osteoprotegerin (OPG), a natural decoy receptor for RANKL. Here, the expression of OPG and RANKL in primary mouse osteoblastic cultures was investigated to determine whether the osteoclastogenic stimulus depended on the stage of osteoblastic differentiation and the presence of the calciotrophic hormone 1,25OPG mRNA expression was increased in osteoblastic cultures after the onset of mineralisation relative to less mature cultures, but did not alter in response to 1,25-(OH) 2 D 3 treatment. In contrast, basal RANKL mRNA expression did not change during differentiation but was significantly enhanced by 1,25-(OH) 2 D 3 treatment at all times. The stimulatory effects of 1,25-(OH) 2 D 3 on RANKL were lessened in more mature cultures, however. The RANKL/OPG ratio, an index of osteoclastogenic stimulus, was therefore increased by 1,25-(OH) 2 D 3 treatment at all stages of osteoblastic differentiation, but to a lesser degree in cultures after the onset of mineralisation. Thus the 1,25-(OH) 2 D 3 -driven increase in osteoclastogenic potential of immature osteoblasts appears to be mediated by increased RANKL mRNA expression, with mature osteoblasts having relatively decreased osteoclastogenic activity due to increased OPG mRNA expression. These findings suggest a possible mechanism for the recently proposed negative regulatory role of mature osteoblasts on osteoclastogenesis and indicate that the relative proportions of immature and mature osteoblasts in the local microenvironment may control the degree of resorption at each specific bone site.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts

Thomas

Baker

Eisman³

et al. 2001

Journal of Endocrinology

165

114

View full text Add to dashboard Cite

show abstract

“…Osteoclast formation and maturation are promoted by a production ratio of RANKL versus osteoprotegerin (OPG; a decoy receptor for RANKL secreted by stromal cells; also referred to as osteoclastogenesis inhibitory factor, OCIF) following stimulation of osteoblastic stromal cells by osteotropic factors such as 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), para thyroid hormone (PTH), or interleukin 11 (IL-11) [15,16]. Therefore, osteoclastogenesis is regulated by interaction with stromal cells and stimulation involving several osteotropic factors.…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase 4 inhibitor rolipram potentiates the inhibitory effect of calcitonin on osteoclastogenesis

et al. 2006

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To assess the combination effect of calcitonin and the phosphodiesterase 4 inhibitor rolipram on osteoclastogenesis, adherent cell-depleted bone marrow cells from mouse tibia and femur (ACD-BMCs), which were cultured in the presence of 25 ng/ml colony-stimulating factor 1 (CSF-1) and 100 ng/ml soluble receptor activator of NF-κB ligand (sRANKL), were utilized. Calcitonin inhibited formation of tartrate-resistant acid phosphatasepositive multinucleated cells, as mature osteoclasts, by 70% even at 20 pM, whereas rolipram (10 µM) scarcely affected osteoclast formation; in contrast, the combination of both agents led to significant inhibition of multinucleation and pit formation ability of osteoclasts. The combined administration of calcitonin and rolipram attenuated calcitonin receptor mRNA expression in comparison to treatment with either agent alone, whereas expression of RANK and CSF-1 receptor mRNAs was unchanged. Alone, these agents scarcely elevated intracellular cyclic AMP (cAMP) concentration; however, combination treatment with both agents significantly increased cAMP concentration in osteoclast progenitors and osteoclasts. The combination effect was abolished by H-89, an inhibitor of protein kinase A. It appears that rolipram inhibited hydrolysis of cAMP formed by calcitonin in cells and potentiated the inhibitory effect of calcitonin on osteoclastogenesis. The escape phenomenon following calcitonin treatment may also be prevented by concomitant treatment with the phosphodiesterase 4 inhibitor.

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Skeletogenesis: Genetics

Wuelling

Vortkamp

2013

Encyclopedia of Life Sciences

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The vertebrate skeleton is formed by two mechanisms – endochondral and intramembranous ossification. During intramembranous ossification, mesenchymal cells directly differentiate into osteoblasts. Endochondral ossification is a two‐step process during which bones are preformed as cartilage templates, which are subsequently replaced by bone. During this process, the inner cells of the cartilage condensation differentiate into chondrocytes, which proliferate and differentiate into hypertrophic chondrocytes producing a mineralised matrix. The outer cells differentiate into the perichondrium surrounding the cartilage template and later into osteoblasts, which produce a bone collar surrounding the hypertrophic region. Blood vessels from the bone collar invade the hypertrophic region in close association with bone‐resorbing osteoclasts and bone‐forming osteoblasts. The orchestrated formation, differentiation and degradation of cartilage and bone are regulated by a multitude of growth factors and transcriptional regulators, which will be discussed in this article. Key Concepts: During intramembranous ossification, mesenchymal progenitor cells differentiate directly into bone‐forming osteoblasts. Endochondral ossification includes the formation of cartilage templates, which are subsequently replaced by bone and bone marrow. Cells in the cartilage condensation represent bipotential osteochondroprogenitor cells that differentiate depending on their level of Sox9 into chondrocytes. Ihh serves as a key regulator of endochondral ossification regulating chondrocyte proliferation, hypertrophic differentiation and ossification. Ihh and Pthrp interact in a negative feedback mechanism to control the domain of columnar, high‐proliferating chondrocytes. Pthrp negatively regulates cell cycle exit. Runx2 and Mef2c activate chondrocyte differentiation. Runx2 and Osterix are required to induce osteoblast differentiation. The balance between Rankl and osteoprotegerin determines the differentiation of osteoclasts. Chondrocyte differentiation is regulated by secreted growth factors, which activate distinct steps of the differentiation programme.

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Reciprocal Gene Expression of Osteoclastogenesis Inhibitory Factor and Osteoclast Differentiation Factor Regulates Osteoclast Formation

Cited by 103 publications

References 21 publications

Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts

Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts

Phosphodiesterase 4 inhibitor rolipram potentiates the inhibitory effect of calcitonin on osteoclastogenesis

Skeletogenesis: Genetics

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