Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

Pfeilschifter, Johannes; Seyedin, Saeid M.; Mundy, Gregory R.

doi:10.1172/jci113647

Cited by 256 publications

(77 citation statements)

References 33 publications

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“…32 PSA-mediated proteolysis of the small latent tumor growth factor-b2 results in activation of tumor growth factor-b, 18 another important stimulator of new bone formation. 33,34 Bone histomorphometric parameters are indicative of bone reactions. Increases in the number of osteoblasts and the amount of osteoid are indicative of osteoblastic reactions, whereas increases in the number of osteoclasts and the amount of resorbed or eroded surface are observed in osteolysis.…”

Section: Discussionmentioning

confidence: 99%

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Cumming

Hopmans

Vukmirović-Popović

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND:Patients with advanced prostate cancer frequently have a poor prognosis as a result of metastasis and present with high serum PSA levels. There is evidence suggesting that the serine protease activity of PSA could be involved in the invasion and metastasis of prostate cancer. In this study, we determined the effects of PSA and its precursor, pro-PSA, on invasion and the type of bone metastasis. METHODS:We stably transfected prostate adenocarcinoma cells, human DU-145 and rat MatLyLu, with either the fulllength prepro-PSA sequence or pre-PSA DNA, to generate subclones of cells that secrete pro-PSA or free PSA, respectively. Secretion of PSA was measured by western blot analysis and enzyme-linked immunosorbent assay (ELISA). The invasive and migratory properties of the cells were determined using a basement membrane extract and were compared with corresponding empty vector control cells. Twelve days after injection of PSA-secreting MatLyLu cells into the femora of nude mice, bone tumor burden and histomorphometry were determined using a stereological technique. RESULTS:The transfected cells secreted 0.15-2.23 ng PSA/10 6 cells/day. Pro-PSA-secreting subclones increased invasion and migration by 24-263%. Conversely, the PSA-secreting subclones significantly reduced both invasion and migration by 59-70%. The divergent effects on invasion and migration observed in pro-PSA-and PSA-secreting subclones indicate that different forms of PSA may have different functions. Intrafemoral injections with PSA-secreting MatLyLu cells resulted in an increase in osteoblastic parameters when compared with non-PSA-secreting subclones as measured by bone histomorphometry. Concomitantly, a decrease in osteoclasts and eroded surface was observed.CONCLUSIONS: Our in vitro data suggest that PSA, dependent on the predominant form secreted, may decrease or increase invasive properties of prostate cancer cells. The in vivo results indicate that PSA in the bone microenvironment may contribute to the osteoblastic phenotype of bone metastasis frequently observed in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Cumming

Hopmans

Vukmirović-Popović

et al. 2011

Prostate Cancer Prostatic Dis

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“…Transforming growth factor-b (TGF-b) which inhibits osteoclastic bone resorption (42,43) was also found to stimulate the production of OPG/OCIF by various bone marrow stromal cell lines and primary osteoblasts, and subsequently to inhibit osteoclastogenesis (40,44). Moreover, the inhibitory effects of TGF-b on osteoclastogenesis were prevented by treatment with an OPG/ OCIF neutralizing antibody, suggesting direct mediation of the anti-resorptive effects of TGF-b by OPG/OCIF (40,44).…”

Section: Regulation Of Opg/ocif By Systemic Hormones and Factorsmentioning

confidence: 99%

Osteoprotegerin ligand and osteoprotegerin: novel implications for osteoclast biology and bone metabolism

Hofbauer

1999

European Journal of Endocrinology

112

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“…In addition, exogenous TGF-␤ induced the further commitment and maturation of osteoclast progenitors into mature osteoclasts in the absence of stromal cells. In contrast, many studies using in vitro culture systems containing stromal cells have demonstrated that TGF-␤ inhibited the differentiation and function of osteoclasts (13,14). Thus, TGF-␤ possesses multifunctional biological activities.…”

mentioning

confidence: 97%

Endogenous Production of TGF-β Is Essential for Osteoclastogenesis Induced by a Combination of Receptor Activator of NF-κB Ligand and Macrophage-Colony- Stimulating Factor

Kaneda

Nojima

Nakagawa

et al. 2000

The Journal of Immunology

112

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Differentiation of osteoclasts, the cells primarily responsible for bone resorption, is controlled by a variety of osteotropic hormones and cytokines. Of these factors, receptor activator of NF-κB (RANK) ligand (RANKL) has been recently cloned as an essential inducer of osteoclastogenesis in the presence of M-CSF. Here, we isolated a stroma-free population of monocyte/macrophage (M/Mφ)-like hemopoietic cells from mouse unfractionated bone cells that were capable of differentiating into mature osteoclasts by treatment with soluble RANKL (sRANKL) and M-CSF. However, the efficiency of osteoclast formation was low, suggesting the requirement for additional factors. The isolated M/Mφ-like hemopoietic cells expressed TGF-β and type I and II receptors of TGF-β. Therefore, we examined the effect of TGF-β on osteoclastogenesis. TGF-β with a combination of sRANKL and M-CSF promoted the differentiation of nearly all M/Mφ-like hemopoietic cells into cells of the osteoclast lineage. Neutralizing anti-TGF-β Ab abrogated the osteoclast generation. These TGF-β effects were also observed in cultures of unfractionated bone cells, and anti-TGF-β blocked the stimulatory effect of 1,25-dihydroxyvitamin D3. Translocation of NF-κB into nuclei induced by sRANKL in TGF-β-pretreated M/Mφ-like hemopoietic cells was greater than that in untreated cells, whereas TGF-β did not up-regulate the expression of RANK, the receptor of RANKL. Our findings suggest that TGF-β is an essential autocrine factor for osteoclastogenesis.

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Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

Cited by 256 publications

References 33 publications

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Osteoprotegerin ligand and osteoprotegerin: novel implications for osteoclast biology and bone metabolism

Endogenous Production of TGF-β Is Essential for Osteoclastogenesis Induced by a Combination of Receptor Activator of NF-κB Ligand and Macrophage-Colony- Stimulating Factor

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