Parathyroid-blunting protein is valid osteoporosis target
MedWire News: Nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) suppresses bone growth stimulated by parathyroid hormone (PTH), say scientists who believe their findings have important implications for osteoporosis therapy.
"PTH is the only osteoporosis treatment that restores bone to the aged skeleton; however, its expense makes it the least cost-effective," write Joseph Bidwell (Indiana University, Indianapolis, USA) and co-workers.
"The development of shorter PTH-based treatments yielding similar efficacy as the longer-term therapy will improve its cost-benefit ratio, but this requires a better understanding of the mechanisms underlying the parathyroid hormone anabolic response," the investigators add.
In previous research, Bidwell and colleagues demonstrated that disabling Nmp4/CIZ enhances the effect of PTH on the skeletons of mice, suggesting that the factor is a general suppressor of anabolic bone growth.
To validate this finding, the researchers studied young mice lacking the Nmp4 gene. These mice together with wild-type mice were treated with PTH 30 µg/kg/day or placebo for 2, 3, or 7 weeks.
As reported in the journal Calcified Tissue International, mice lacking Nmp4 gained significantly more bone throughout the skeleton in response to PTH treatment than did wild-type mice. Interestingly, this difference only became evident after 7 weeks of treatment.
Further analysis showed that suppression of Nmp4 expression led to increased expression of various genes that are central to the development of both osteoblasts and osteoclasts.
Surprisingly, mice lacking Nmp4 were shown to have an osteoclast phenotype, with raised levels of the bone resorption marker C-terminal telopeptide, regardless of whether PTH treatment was given or not.
The authors write: "We propose that Nmp4/CIZ governs both the osteoblast and osteoclast cellular arms of the parathyroid hormone-induced anabolic response by controlling the size, activity, and/or parathyroid hormone responsiveness of these cell populations, in part via the modest suppression of several key transcription factors and receptors critical to the developmental and/or response pathways of both cells."
Although Bidwell and colleagues concede that further research is necessary to better understand the complex sequence of molecular and cellular events underpinning the effects of Nmp4/CIZ on bone re-modelling, they say they are optimistic about the potential of Nmp4/CIZ inhibition as a therapeutic strategy for osteoporosis.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Philip Ford