Mice lacking the integrin β5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state

Nancy E Lane, Wei Yao, Mary C. Nakamura, Mary Beth Humphrey, Donald Kimmel, Xiaozhu Huang, Dean Sheppard, F. Patrick Ross, Steven L. Teitelbaum

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    Integrin αvβ5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as αvβ3. Three-month-old β5-/- female OVX mice had increased osteoclastogenesis ex vivo, and μCT assessment of trabecular bone volume was 53% lower than WT-OVX animals. These preliminary data suggest αvβ5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation. Introduction: Osteoclasts are unique resorptive skeletal cells, capable of degrading bone on contact to the juxtaposed matrix. Integrin αv;β5 is expressed on osteoclast precursors, structurally similar to αvβ3, and capable of recognizing the same amino acid motif. Given the structural relationship and reciprocal regulation of αvβ3 and αvβ5, the purpose of this study was to evaluate how αvβ5 might contribute to osteoclast maturation and activity. Materials and Methods: Three-month-old wildtype (WT) and β5-/- female mice had ovariectomy (OVX) or sham operations. The osteoclastogenic capacity of marrow-derived precursors, the kinetic, the circulating, and structural parameters of bone remodeling, was determined after 6 weeks of paired feeding. Results and Conclusions: OVX increased osteoclastogenesis ex vivo and in vivo. Osteoclast formation and prolonged pre-osteoclast survival were substantially enhanced in cultures containing β5-/- cells whether obtained from sham-operated or OVX mice. Expression of cathepsin K, β3 integrin subunit, and calcitonin receptor were accelerated in cultured β5 -/- osteoclasts. β5-/- osteoclasts from OVX animals showed a 3-fold enhancement of net resorptive activity, with quantitative ìËÊshowing trabecular bone volume loss after OVX 53% greater in β5-/- OVX compared with similarly treated WT OVX mice (p < 0.05). α5β3 seems to be an inhibitor of osteoclast formation, in contrast to αvβ3. In addition, loss of αvβ5 seems to accelerate osteoclast formation in the OVX model. Further examination of αvβ5 signaling pathways may enhance our understanding of the activation of bone resorption.

    Original languageEnglish (US)
    Pages (from-to)58-66
    Number of pages9
    JournalJournal of Bone and Mineral Research
    Volume20
    Issue number1
    DOIs
    StatePublished - 2005

    Fingerprint

    Osteoclasts
    Integrins
    Estrogens
    Amino Acid Motifs
    Osteogenesis
    Calcitonin Receptors
    Cathepsin K
    Bone Remodeling
    Ovariectomy
    Bone Resorption
    Bone Marrow
    Bone and Bones

    Keywords

    • β5-knockout
    • Estrogen deficiency
    • Mice
    • Osteoclasts

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Mice lacking the integrin β5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. / Lane, Nancy E; Yao, Wei; Nakamura, Mary C.; Humphrey, Mary Beth; Kimmel, Donald; Huang, Xiaozhu; Sheppard, Dean; Ross, F. Patrick; Teitelbaum, Steven L.

    In: Journal of Bone and Mineral Research, Vol. 20, No. 1, 2005, p. 58-66.

    Research output: Contribution to journalArticle

    Lane, Nancy E ; Yao, Wei ; Nakamura, Mary C. ; Humphrey, Mary Beth ; Kimmel, Donald ; Huang, Xiaozhu ; Sheppard, Dean ; Ross, F. Patrick ; Teitelbaum, Steven L. / Mice lacking the integrin β5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. In: Journal of Bone and Mineral Research. 2005 ; Vol. 20, No. 1. pp. 58-66.
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    abstract = "Integrin αvβ5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as αvβ3. Three-month-old β5-/- female OVX mice had increased osteoclastogenesis ex vivo, and μCT assessment of trabecular bone volume was 53{\%} lower than WT-OVX animals. These preliminary data suggest αvβ5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation. Introduction: Osteoclasts are unique resorptive skeletal cells, capable of degrading bone on contact to the juxtaposed matrix. Integrin αv;β5 is expressed on osteoclast precursors, structurally similar to αvβ3, and capable of recognizing the same amino acid motif. Given the structural relationship and reciprocal regulation of αvβ3 and αvβ5, the purpose of this study was to evaluate how αvβ5 might contribute to osteoclast maturation and activity. Materials and Methods: Three-month-old wildtype (WT) and β5-/- female mice had ovariectomy (OVX) or sham operations. The osteoclastogenic capacity of marrow-derived precursors, the kinetic, the circulating, and structural parameters of bone remodeling, was determined after 6 weeks of paired feeding. Results and Conclusions: OVX increased osteoclastogenesis ex vivo and in vivo. Osteoclast formation and prolonged pre-osteoclast survival were substantially enhanced in cultures containing β5-/- cells whether obtained from sham-operated or OVX mice. Expression of cathepsin K, β3 integrin subunit, and calcitonin receptor were accelerated in cultured β5 -/- osteoclasts. β5-/- osteoclasts from OVX animals showed a 3-fold enhancement of net resorptive activity, with quantitative {\`i}{\"E}{\^E}showing trabecular bone volume loss after OVX 53{\%} greater in β5-/- OVX compared with similarly treated WT OVX mice (p < 0.05). α5β3 seems to be an inhibitor of osteoclast formation, in contrast to αvβ3. In addition, loss of αvβ5 seems to accelerate osteoclast formation in the OVX model. Further examination of αvβ5 signaling pathways may enhance our understanding of the activation of bone resorption.",
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    AU - Lane, Nancy E

    AU - Yao, Wei

    AU - Nakamura, Mary C.

    AU - Humphrey, Mary Beth

    AU - Kimmel, Donald

    AU - Huang, Xiaozhu

    AU - Sheppard, Dean

    AU - Ross, F. Patrick

    AU - Teitelbaum, Steven L.

    PY - 2005

    Y1 - 2005

    N2 - Integrin αvβ5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as αvβ3. Three-month-old β5-/- female OVX mice had increased osteoclastogenesis ex vivo, and μCT assessment of trabecular bone volume was 53% lower than WT-OVX animals. These preliminary data suggest αvβ5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation. Introduction: Osteoclasts are unique resorptive skeletal cells, capable of degrading bone on contact to the juxtaposed matrix. Integrin αv;β5 is expressed on osteoclast precursors, structurally similar to αvβ3, and capable of recognizing the same amino acid motif. Given the structural relationship and reciprocal regulation of αvβ3 and αvβ5, the purpose of this study was to evaluate how αvβ5 might contribute to osteoclast maturation and activity. Materials and Methods: Three-month-old wildtype (WT) and β5-/- female mice had ovariectomy (OVX) or sham operations. The osteoclastogenic capacity of marrow-derived precursors, the kinetic, the circulating, and structural parameters of bone remodeling, was determined after 6 weeks of paired feeding. Results and Conclusions: OVX increased osteoclastogenesis ex vivo and in vivo. Osteoclast formation and prolonged pre-osteoclast survival were substantially enhanced in cultures containing β5-/- cells whether obtained from sham-operated or OVX mice. Expression of cathepsin K, β3 integrin subunit, and calcitonin receptor were accelerated in cultured β5 -/- osteoclasts. β5-/- osteoclasts from OVX animals showed a 3-fold enhancement of net resorptive activity, with quantitative ìËÊshowing trabecular bone volume loss after OVX 53% greater in β5-/- OVX compared with similarly treated WT OVX mice (p < 0.05). α5β3 seems to be an inhibitor of osteoclast formation, in contrast to αvβ3. In addition, loss of αvβ5 seems to accelerate osteoclast formation in the OVX model. Further examination of αvβ5 signaling pathways may enhance our understanding of the activation of bone resorption.

    AB - Integrin αvβ5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as αvβ3. Three-month-old β5-/- female OVX mice had increased osteoclastogenesis ex vivo, and μCT assessment of trabecular bone volume was 53% lower than WT-OVX animals. These preliminary data suggest αvβ5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation. Introduction: Osteoclasts are unique resorptive skeletal cells, capable of degrading bone on contact to the juxtaposed matrix. Integrin αv;β5 is expressed on osteoclast precursors, structurally similar to αvβ3, and capable of recognizing the same amino acid motif. Given the structural relationship and reciprocal regulation of αvβ3 and αvβ5, the purpose of this study was to evaluate how αvβ5 might contribute to osteoclast maturation and activity. Materials and Methods: Three-month-old wildtype (WT) and β5-/- female mice had ovariectomy (OVX) or sham operations. The osteoclastogenic capacity of marrow-derived precursors, the kinetic, the circulating, and structural parameters of bone remodeling, was determined after 6 weeks of paired feeding. Results and Conclusions: OVX increased osteoclastogenesis ex vivo and in vivo. Osteoclast formation and prolonged pre-osteoclast survival were substantially enhanced in cultures containing β5-/- cells whether obtained from sham-operated or OVX mice. Expression of cathepsin K, β3 integrin subunit, and calcitonin receptor were accelerated in cultured β5 -/- osteoclasts. β5-/- osteoclasts from OVX animals showed a 3-fold enhancement of net resorptive activity, with quantitative ìËÊshowing trabecular bone volume loss after OVX 53% greater in β5-/- OVX compared with similarly treated WT OVX mice (p < 0.05). α5β3 seems to be an inhibitor of osteoclast formation, in contrast to αvβ3. In addition, loss of αvβ5 seems to accelerate osteoclast formation in the OVX model. Further examination of αvβ5 signaling pathways may enhance our understanding of the activation of bone resorption.

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