Total Knockdown of LMW-PTP in MDA-MB-231 Cells Reduces Osteoclastogenesis.

Abstract

Low molecular weight protein tyrosine phosphatase (LMW-PTP) has been related to tumorigenesis, having both oncogenic and anti-oncogenic roles. The differential roles of its main active isoforms (fast and slow) may account for these discrepancies. The fast isoform has been described to be involved in the bone-metastatic process, although knockdown of the slow isoform was recently reported to reduce osteoclastogenesis. We aimed to study the influence of LMW-PTP isoforms on osteoclast differentiation. Osteoclast precursors (RAW 264.7) were cultured with conditioned medium from MDA-MB-231 breast cancer cells with total knockdown of LMW-PTP and with knockdown of the slow isoform of LMW-PTP. Tartarate-resistant acid phosphatase (TRAP) staining and quantification were performed to assess osteoclast differentiation. Total knockdown of LMW-PTP, but not of slow LMW-PTP significantly reduced osteoclast differentiation of RAW 264.7 cells. We suggest that total LMW-PTP increases osteoclastic differentiation, albeit not at the expense of the slow isoform.