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  • Börjesson, Anna EGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research (författare)

The role of estrogen receptor-alpha and its activation function-1 for growth plate closure in female mice

  • Artikel/kapitelEngelska2012

Förlag, utgivningsår, omfång ...

  • American Physiological Society,2012

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/160860
  • https://gup.ub.gu.se/publication/160860URI
  • https://doi.org/10.1152/ajpendo.00646.2011DOI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Borjesson AE, Windahl SH, Karimian E, Eriksson EE, Lagerquist MK, Engdahl C, Antal MC, Krust A, Chambon P, Savendahl L, Ohlsson C. The role of estrogen receptor-alpha and its activation function-1 for growth plate closure in female mice. Am J Physiol Endocrinol Metab 302: E1381-E1389, 2012. First published March 13, 2012; doi:10.1152/ajpendo.00646.2011.-High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-alpha stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ER alpha and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ER alpha (ER alpha(-/-)) or ER alpha AF-1 (ER alpha AF-1(0)) were evaluated. Old (16- to 19-mo-old) female ER alpha(-/-) mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ER alpha AF-1(0) mice (tibia: -4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ER alpha AF-1(0) mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ER alpha(-/-) mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ER alpha or aromatase. In contrast, ER alpha AF-1 deletion results in a hyperactive ER alpha, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ER alpha that do not require AF-1 and that ER alpha AF-1 opposes growth plate closure.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Windahl, Sara H,1971Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xwinds (författare)
  • Karimian, E. (författare)
  • Eriksson, E. E. (författare)
  • Lagerquist, MarieGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xlmarv (författare)
  • Engdahl, Cecilia,1983Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xhakce (författare)
  • Antal, M. C. (författare)
  • Krust, A. (författare)
  • Chambon, P. (författare)
  • Savendahl, L. (författare)
  • Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (författare)
  • Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:American Journal of Physiology-Endocrinology and Metabolism: American Physiological Society302:110193-18491522-1555

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