Regulators of chondrocyte differentiation in tibial dyschondroplasia: an in vivo and in vitro study

C Farquharson, J L Berry, E B Mawer, E Seawright, C C Whitehead

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Abstract

Tibial dyschondroplasia (TD) is a disorder of endochondral bone growth and results in the retention of a mass of unmineralized, avascular cartilage extending into the metaphysis. We have studied various parameters of chondrocyte differentiation, both in isolated chick chondrocytes and growth plate sections, in an attempt to determine whether the inhibition in chondrocyte differentiation seen in TD is a consequence of an inherent incapability of chondrocytes to differentiate terminally and mineralize. Results from in vitro experiments indicated that both normal and lesion chondrocytes synthesized a matrix that stained with antibodies to types II and X collagen and displayed foci of mineralization. Alkaline phosphatase activity in lesion chondrocytes was significantly increased in comparison to that in normal hypertrophic chondrocytes. In addition, normal and lesion chondrocytes in culture synthesized transforming growth factor-beta and 24,25(OH)2D3 but not 1,25(OH)2D3. There was no significant difference in the production rate of these growth regulators between normal and lesion chondrocytes. In contrast, in growth plate sections, alkaline phosphatase activity was markedly reduced in the lesion chondrocytes and sites of mineralization were not evident. Type II collagen was located throughout the growth plate and lesion, but type X collagen was not present within the lesion except at sites of vascularization. These results indicate that, in culture, lesion chondrocytes have the ability to differentiate terminally and mineralize, and suggest that the primary abnormality in TD is related to a developmental fault which is only operative in vivo. This may include a defect in cartilage vascularization and/or impairment of chondrocyte differentiation by mechanisms that have not yet been elucidated but may involve the abnormal production of regulatory factors.
Original languageEnglish
Pages (from-to)279-86
Number of pages8
JournalBone
Volume17
Issue number3
Publication statusPublished - Sep 1995

Keywords

  • 24,25-Dihydroxyvitamin D 3
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Alkaline Phosphatase
  • Animals
  • Calcification, Physiologic
  • Calcitriol
  • Cartilage
  • Cell Differentiation
  • Cells, Cultured
  • Chickens
  • Collagen
  • Growth Plate
  • Immunohistochemistry
  • Osteochondrodysplasias
  • Tibia
  • Transforming Growth Factor beta

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