Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation

Masahiro Iwamoto, Akitoshi Jikko, Hiroshi Murakami, Atsushi Shimazu, Kazuhisa Nakashima, Motomi Iwamoto, Masaharu Takigawa, Hisamitsu Baba, Fujio Suzuki, Yukio Kato

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to investigate the relationship between changes in parathyroid hormone (PTH) receptor levels and chondrocyte maturation during endochondral ossification. Chondrocytes were isolated from the growth plate of rabbit ribs and maintained in the presence of 10% serum in mass cultures. Treatment with PTH-(1-84) and a PTH-(1-34) fragment suppressed the increases in alkaline phosphatase activity and in type X collagen and 1α,25-dihydroxyvitamin D3 receptor levels and abolished 45Ca incorporation into mineral, all of which occurred in parallel untreated cultures in the hypertrophic (terminal) stage. These effects of PTH were observed at low concentrations (10-10 to 10-9 M) and within 24-48 h of treatment. PTH-(1-84) and PTH-(1-34) also increased [35S]sulfate incorporation into newly synthesized proteoglycans. In contrast, the middle and carboxyl-terminal fragments of PTH tested had little effect on proteoglycan synthesis or terminal differentiation. The binding of 125I- PTH-(1-34) to cells in the growth plate was greater than that to cells in liver, skin, muscle, brain, or kidney. When the correlation between binding levels and stage of maturation was examined, we found that 125I-PTH-(1- 34) binding to its 72-kDa receptor was low in resting and proliferating chondrocytes, increased 10-fold in matrix-forming chondrocytes, and thereafter decreased in hypertrophic chondrocytes both in vitro and in situ. Scatchard analysis revealed that the changes in PTH binding were due to changes in the number, and not in the affinity, of the receptor. The changes in PTH-(1-34) binding paralleled those in [35S]sulfate incorporation into proteoglycans. These findings suggest that stage-dependent increases in PTH/PTH-related peptide receptor levels localize the hormone stimulation of proteoglycan synthesis and inhibition of precocious hypertrophy in the matrix-forming zone of growth plates.

Original languageEnglish
Pages (from-to)17245-17251
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number25
Publication statusPublished - Jun 24 1994
Externally publishedYes

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Parathyroid Hormone Receptors
Proteoglycans
Chondrocytes
Parathyroid Hormone
Parathyroid Hormone Receptor Type 1
Sulfates
Collagen Type X
Growth Plate
Calcitriol Receptors
Liver
Minerals
Alkaline Phosphatase
Muscle
Brain
Skin
Hormones
Ribs
Osteogenesis
Hypertrophy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Iwamoto, M., Jikko, A., Murakami, H., Shimazu, A., Nakashima, K., Iwamoto, M., ... Kato, Y. (1994). Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. Journal of Biological Chemistry, 269(25), 17245-17251.

Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. / Iwamoto, Masahiro; Jikko, Akitoshi; Murakami, Hiroshi; Shimazu, Atsushi; Nakashima, Kazuhisa; Iwamoto, Motomi; Takigawa, Masaharu; Baba, Hisamitsu; Suzuki, Fujio; Kato, Yukio.

In: Journal of Biological Chemistry, Vol. 269, No. 25, 24.06.1994, p. 17245-17251.

Research output: Contribution to journalArticle

Iwamoto, M, Jikko, A, Murakami, H, Shimazu, A, Nakashima, K, Iwamoto, M, Takigawa, M, Baba, H, Suzuki, F & Kato, Y 1994, 'Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation', Journal of Biological Chemistry, vol. 269, no. 25, pp. 17245-17251.
Iwamoto M, Jikko A, Murakami H, Shimazu A, Nakashima K, Iwamoto M et al. Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. Journal of Biological Chemistry. 1994 Jun 24;269(25):17245-17251.
Iwamoto, Masahiro ; Jikko, Akitoshi ; Murakami, Hiroshi ; Shimazu, Atsushi ; Nakashima, Kazuhisa ; Iwamoto, Motomi ; Takigawa, Masaharu ; Baba, Hisamitsu ; Suzuki, Fujio ; Kato, Yukio. / Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 25. pp. 17245-17251.
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