Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate

V. Lezcano, T. Bellido, L. I. Plotkin, R. Boland, S. Morelli

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [3H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPμ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPμ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.

Original languageEnglish (US)
Pages (from-to)30-39
Number of pages10
JournalExperimental Cell Research
Volume324
Issue number1
DOIs
StatePublished - May 15 2014

Fingerprint

Alendronate
Connexin 43
Protein Tyrosine Phosphatases
Diphosphonates
Phosphorylation
Osteoblasts
Phosphoric Monoester Hydrolases
Tyrosine
Bone Density Conservation Agents
Osteocytes
Extracellular Signal-Regulated MAP Kinases
Osteoclasts
Catalytic Domain
Binding Sites
Apoptosis
Proteins

Keywords

  • Alendronate
  • Cx43 hemichannels
  • Osteoblasts
  • Protein tyrosine phosphatases

ASJC Scopus subject areas

  • Cell Biology

Cite this

Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate. / Lezcano, V.; Bellido, T.; Plotkin, L. I.; Boland, R.; Morelli, S.

In: Experimental Cell Research, Vol. 324, No. 1, 15.05.2014, p. 30-39.

Research output: Contribution to journalArticle

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AU - Morelli, S.

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