Biomedical subjects

Edith Bonnelye

Publications and source records attributed to Edith Bonnelye.

4 recordsLinked to original sources

PubMed2006

Transmigration: a new property of mature multinucleated osteoclasts.

UNLABELLED: Even though it is assumed that multinucleated osteoclasts are migrating cells on the bone surface to be resorbed, we show that they can also selectively transmigrate through layers of cells usually found in the bone microenvironment. This activity is associated with c-src and MMPs and can be stimulated by bone metastatic breast cancer cells, a process blocked by bisphosphonate treatment. INTRODUCTION: Osteoclasts have an hematopoietic origin and are bone-resorbing cells. Monocytic precursors migrate to the bone surface where they fuse to form multinucleated osteoclasts able to migrate over the bone surface. We studied whether multinucleated osteoclasts were also able to transmigrate through tissues. MATERIALS AND METHODS: Murine spleen-derived and green fluorescent protein (GFP)-Raw derived osteoclasts were seeded on osteoblasts and several other cell types. The cells were fixed for 20 minutes, 4 or 12 h after osteoclast seeding, and stained with phalloidin to visualize actin using confocal microscopy. Drugs such as PP2 and GM6001, inhibitors of c-src and matrix metalloproteinases (MMPs), respectively, and risedronate were used to determine osteoclast transmigration regulating factors. RESULTS: We observed by confocal microscopy that multinucleated osteoclasts specifically transmigrate through confluent layers of various cell types present in the bone microenvironment in vitro. This is an efficient process associated with c-src and MMPs but is independent of podosomes. Moreover, conditioned medium from bone metastatic breast cancer cells stimulates osteoclast transmigration in vitro, a process inhibited by bisphosphonate treatment. CONCLUSIONS: Our data describe a new property of mature multinucleated osteoclasts to transmigrate through various cell types. The ability to control this highly regulated osteoclast transmigration process may offer new therapeutic strategies for bone diseases associated with an imbalance in bone remodeling caused by excessive osteoclast resorption.

Animals↗

PubMed2005

Expression and function of semaphorin 7A in bone cells.

BACKGROUND INFORMATION: Sema-7A is a glycosylphosphatidylinositol-anchored semaphorin that was first identified in the immune system. It is a member of a large family of proteins involved in axon guidance signalling. Sema-7A is expressed in the myeloid and the lymphoid lineage and seems to be involved in cytokine expression and chemotaxy through its receptor Plexin C1. However, it can promote axon outgrowth, acting through a beta1 subunit-containing integrin receptor. RESULTS AND CONCLUSIONS: In the present study, we have investigated its regulation and function in bone cells. Semiquantitative reverse transcriptase-PCR demonstrated that Sema-7A mRNA is present during all stages of osteoblast differentiation and maturation in mouse calvaria cells and in MC3T3 cell line in vitro. Its expression is also regulated during primary osteoclast differentiation in vitro. We report that Sema-7A is capable of increasing the migration of MC3T3 cells and that this process is mediated by the mitogen-activated protein kinase pathway in osteoblasts, probably through the integrin subunit beta1. Moreover, the addition of recombinant soluble Sema-7A to the culture enhances osteoclast fusion. These findings indicate for the first time the possible involvement of Sema-7A in bone cell differentiation.

Animals↗

PubMed2002

Estrogen receptor-related receptor alpha impinges on the estrogen axis in bone: potential function in osteoporosis.

The orphan nuclear estrogen receptor-related receptor alpha (ERRalpha) is expressed by osteoblastic cells and plays a functional role in osteoprogenitor proliferation and differentiation. To dissect further the role of ERRalpha in bone, we investigated the effects of estrogen (E2) on ERRalpha both in vitro and in vivo. Chronic treatment of fetal rat calvaria cells with E2-stimulated bone nodule formation and up-regulated ERRalpha mRNA expression at early (10 h and d 8) but not later times in culture, suggesting a link between ERRalpha and E2 during osteoprogenitor proliferation. ERRalpha mRNA levels were significantly lower in ovariectomized adult rat bones vs. those of sham-operated rats early (1 d and 1 wk) post surgery, but levels returned to control levels thereafter. ERRalpha is also expressed in osteoclasts (tartrate-resistant acid phosphatase + multinucleated cells) in vivo and in vitro (RAW 264.7 cells) and ovariectomization lowered the OPG/receptor activator of nuclear factor kappaB ligand expression ratio. Down-regulation of ERRalpha expression via antisense treatment of rat calvaria cells not only inhibited osteogenesis but also increased adipocyte colony formation and changed the OPG/receptor activator of nuclear factor kappaB ligand ratio. These data suggest that ERRalpha is regulated by estrogen in bone in which it may play a functional role at several levels (osteoblasts, adipocytes, and osteoclasts) in E2 deficiency diseases such as osteoporosis.

Adipocytes↗

PubMed2002

Differential expression of estrogen receptor-related receptor alpha and estrogen receptors alpha and beta in osteoblasts in vivo and in vitro.

The orphan nuclear estrogen receptor-related receptor (ERR) alpha is expressed by osteoblastic cells, is known to transactivate at least one osteoblast-associated gene osteopontin (OPN) and plays a functional role in osteoprogenitor cell proliferation and differentiation. To dissect further the role of ERR-alpha in bone formation, we compared its expression to that of the estrogen receptor (ER) alpha and ER-beta in rat calvaria (RC) and fetal tibia in vivo and in RC and rat bone marrow (RBM) cells in vitro. We found that ERR-alpha is highly and widely expressed in most, if not all, cells in RC cell cultures from early proliferation stages through mineralized nodule formation; ER-alpha was localized similarly but at lower levels and ER-beta, although present, was barely detectable. These patterns of expression in vitro correlated with what we observed in vivo in sections of 21-day fetal RC, in which ERR-alpha appeared to be more highly expressed than either of the ERs. Interestingly, ERR-a also is highly expressed in RBM cells, while ER-alpha and ER-beta mRNA is expressed, but at lower levels. Moreover, we found that ERR-alpha, ER-alpha, and ER-beta were all expressed in osteoblasts in fetal and adult tibia whereas they were expressed differentially in calvaria in vivo in subsets of osteoblasts, supporting the hypothesis that ERR-alpha may interact with one or both of the ERs in those osteoblasts in which they are coexpressed and that all three receptors may be required for bone formation but at different times and for different functions.

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