A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis

Lara Longobardi, Monica Torello, Caroline Buckway, Lynda O'Rear, William A. Horton, Vivian Hwa, Charles Roberts, Francesco Chiarelli, Ronald (Ron) Rosenfeld, Anna Spagnoli

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Abstract

Chondrogenesis results from the condensation of mesenchymal chondroprogenitor cells (MCC) that proliferate and differentiate into chondrocytes. We have previously shown that IGF binding protein (IGFBP)-3 has an IGF-independent anti-proliferative effect in MCC. The current study evaluates the IGF-independent apoptotic effect of IGFBP-3 on MCC to modulate chondrocyte differentiation. We employed the RCJ3.1C5.18 chondrogenic cell line, which in culture progresses from MCC to differentiated chondrocytes; cells do not express IGFs or IGFBP-3. We also used IGFBP-3 mutants with decreased (I56 substituted to G56; L80 and L81 to G80G81) or abolished binding for IGFs (I56, L80, and L81 to G56G80G81). MCC transfected with IGFBP-3 detached, changed their phenotype, and underwent apoptosis. A maximal IGFBP-3 apoptotic effect was observed 24 h after transfection (463 ± 73% of controls; P <0.001). Remarkably, IGFBP-3 mutants had similar effects, demonstrating that the IGFBP-3 apoptotic action was clearly IGF independent. In addition, treatment with IGFBP-3 in serum-free conditions resulted in a significant increase of apoptosis (173 ± 23% of controls; P <0.05). Moreover, this apoptotic effect was selective for MCC, resulting in a selective reduction of chondrocytic nodules and a significant decrease in type II collagen expression and proteoglycan synthesis. In summary, we have identified a novel IGF-independent role for IGFBP-3 in the modulation of chondrocyte differentiation.

Original languageEnglish (US)
Pages (from-to)1695-1702
Number of pages8
JournalEndocrinology
Volume144
Issue number5
DOIs
StatePublished - May 1 2003

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Insulin-Like Growth Factor Binding Protein 3
Somatomedins
Apoptosis
Chondrocytes
Chondrogenesis
Collagen Type II
Proteoglycans
Transfection
Phenotype
Cell Line

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Longobardi, L., Torello, M., Buckway, C., O'Rear, L., Horton, W. A., Hwa, V., ... Spagnoli, A. (2003). A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis. Endocrinology, 144(5), 1695-1702. https://doi.org/10.1210/en.2002-220959

A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis. / Longobardi, Lara; Torello, Monica; Buckway, Caroline; O'Rear, Lynda; Horton, William A.; Hwa, Vivian; Roberts, Charles; Chiarelli, Francesco; Rosenfeld, Ronald (Ron); Spagnoli, Anna.

In: Endocrinology, Vol. 144, No. 5, 01.05.2003, p. 1695-1702.

Research output: Contribution to journalArticle

Longobardi, L, Torello, M, Buckway, C, O'Rear, L, Horton, WA, Hwa, V, Roberts, C, Chiarelli, F, Rosenfeld, RR & Spagnoli, A 2003, 'A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis', Endocrinology, vol. 144, no. 5, pp. 1695-1702. https://doi.org/10.1210/en.2002-220959
Longobardi, Lara ; Torello, Monica ; Buckway, Caroline ; O'Rear, Lynda ; Horton, William A. ; Hwa, Vivian ; Roberts, Charles ; Chiarelli, Francesco ; Rosenfeld, Ronald (Ron) ; Spagnoli, Anna. / A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis. In: Endocrinology. 2003 ; Vol. 144, No. 5. pp. 1695-1702.
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AU - Horton, William A.

AU - Hwa, Vivian

AU - Roberts, Charles

AU - Chiarelli, Francesco

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