Caveolin-Enriched Membrane Signaling Complexes in Human and Murine Osteoblasts

Solomon, Keith R.; Danciu, Theodora E.; Adolphson, Layla D.; Hecht, Leah; Hauschka, Peter V.

doi:10.1359/jbmr.2000.15.12.2380

Cited by 37 publications

(32 citation statements)

References 46 publications

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“…Similar findings are corroborated in osteoblastic outgrowths from normal adult bone (Lofthouse et al, 2001). Bone cell caveolae are associated with important signaling molecules including G-proteins, Ras, nitric oxide synthase, and tyrosine kinases (Solomon et al, 2000b). These membrane domains, whether caveolae or non-caveolar lipid rafts, likely provide a microenvironment that enhances both efficiency and fidelity of signal transduction.…”

Section: Membrane Structuresupporting

confidence: 61%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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Section: Membrane Structuresupporting

confidence: 61%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

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“…Osteoblasts have caveolae and express both Cav-1 and Cav-2 isoforms (16). It has been noted that faster-growing osteoblasts have less caveolae (16) and that Cav-1 expression increases along osteoblastic differentiation (12). So we wondered if osteoblast transformation was associated to Cav-1 change of expression.…”

Section: Resultsmentioning

confidence: 97%

“…Cancer Res 2007; 67: (16 osteosarcoma cells to establish lung metastases depending on Cav-1 expression. Cav-1-deficient osteosarcoma cells inoculated i.v.…”

Section: Cancer Researchmentioning

confidence: 99%

“…To search for such signature, we did a microarray analysis of genes involved in modulation of osteosarcoma malignancy by comparing osteosarcoma cell lines with different metastasis behavior and identified caveolin-1 (Cav-1) gene whose expression correlates with a lower metastasis potential (12,13). Cav-1 is the major protein component of caveolae (14), which are abundant in terminally differentiated mesenchymal cells, including adipocytes, endothelial cells, fibroblasts (15), and osteoblasts (16,17). Caveolae provide physical interaction and compartmentalization of several membrane receptors.…”

Section: Introductionmentioning

confidence: 99%

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Caveolin-1 Reduces Osteosarcoma Metastases by Inhibiting c-Src Activity and Met Signaling

et al. 2007

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Caveolin-1 (Cav-1) is highly expressed in normal osteoblasts. This article reports that Cav-1 down-regulation is part of osteoblast transformation and osteosarcoma progression and validates its role as oncosuppressor in human osteosarcoma. A survey of 6-year follow-up indicates a better overall survival for osteosarcoma expressing a level of Cav-1 similar to osteoblasts. However, the majority of primary osteosarcoma shows significantly lower levels of Cav-1 than normal osteoblasts. Accordingly, Met-induced osteoblast transformation is associated with Cav-1 down-regulation. In vitro, osteosarcoma cell lines forced to overexpress Cav-1 show reduced malignancy with inhibited anchorage-independent growth, migration, and invasion. In vivo, Cav-1 overexpression abrogates the metastatic ability of osteosarcoma cells. c-Src and c-Met tyrosine kinases, which are activated in osteosarcoma, colocalize with Cav-1 and are inhibited on Cav-1 overexpression. Thus, Cav-1 behaves as an oncosuppressor in osteosarcoma. Altogether, data suggest that Cav-1 downmodulation might function as a permissive mechanism, which, by unleashing c-Src and Met signaling, enables osteosarcoma cells to invade neighboring tissues. These data strengthen the rationale to target c-Src family kinases and/or Met receptor to improve the extremely poor prognosis of metastatic osteosarcoma. [Cancer Res 2007;67(16):7675-85]

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“…Caveolae are found in a variety of cell types, including neuronal, endothelial, and osteoblastic cells (Toran-Allerand et al, 1999;Solomon et al, 2000). ER␣ co-immunoprecipitates with caveolin-1 (Schlegel et al, 1999).…”

Section: Effects Of Sex Steroids On Osteoblast and Osteocyte Apopmentioning

confidence: 99%

Senior Author Correspondence Information

2002

Recent Progress in Hormone Research

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In mammals, sex is determined by the presence or absence of a single gene on the Y chromosome, Sry. Sry, a member of the high mobility group family of transcription factors, is required to initiate male-specific pathways and repress female-specific pathways. Expression of Sry in the gonad, beginning at 10.5 days postcoitum, leads to the differentiation of the somatic supporting cell precursors as Sertoli cells. These cells direct the other cells of the gonad into their respective lineages. Currently, no direct targets of Sry are known. A number of cellular pathways initiated by Sry are required for testis development. These include the proliferation of pre-Sertoli cells and commitment to the Sertoli lineage, migration of cells from the adjacent mesonephros, and formation of a male-specific vasculature. Work is underway to identify genes controlling these processes. These genes will then be linked to Sry.

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Caveolin-Enriched Membrane Signaling Complexes in Human and Murine Osteoblasts

Cited by 37 publications

References 46 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Caveolin-1 Reduces Osteosarcoma Metastases by Inhibiting c-Src Activity and Met Signaling

Senior Author Correspondence Information

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