Summary of the project
Bone morphogenetic proteins (BMPs) are used locally for treating bone defects in men. We have recently demonstrated that systemically administered BMP-6 restores bone in aged osteoporotic rats (1). However, mechanisms of both the endogenous and systemically administrated BMP-6 in bone formation have not been fully elucidated. The function of endogenous BMP-6 will be explained by using BMP-6 knock-out (Bmp-6 -/-) mice that spontaneously develop osteoporosis (preliminary data). Crosstalk with antiresorptive and anabolic signalling pathways involved in bone remodelling will be tested by estradiol (E2), parathyroid hormone (PTH) and BMP-6 treatment of ovariectomized (OVX) Bmp-6 -/- and wild type (WT) mice and potential requirement of endogenous BMP-6 for treatment of osteoporosis will be disclosed. The interplay between E2, PTH and BMP-6 will be further investigated by protein profiling of WT and Bmp-6 -/- mesenchymal stem cells (MSC). The role of exogenously administered BMP-6 on bones will be examined by pQCT, μCT, histology, biomechanics, gene microarray, RT-PCR, analyses of osteoblasts, osteoclasts, MSC and subsequently serum bone turnover markers. The results will disclose the BMP-6 anabolic effect on bone with a potential for treating osteoporosis. Since the fractures are frequent features of osteoporosis, the effect of BMP-6 on fracture healing will be studied in OVX Bmp-6 -/- and WT femoral fracture model. The possibility of BMP-6 oral delivery will also be investigated by the addition of gastrointestinal enzyme inhibitors, absorption enhancers and buffers. The role of endogenous BMP-6 in humans will be investigated by measuring BMP-6 in blood of healthy and osteoporotic women by matrix-assisted laser desorption ionization time-of-flight protein profiling. The project will develop a strategy for treating osteoporosis and related fractures based on BMP-6 biology. The results of this project will serve as a basis to find commercial partners for clinical multi-centre studies to evaluate the effect of BMP-6 therapy in patients with osteoporosis.
Target groups:
To our knowledge an estimated 75 million people have osteoporosis and global market is worth 5.6 bn € with a forecast to grow to 10.5 bn € by 2011 with predomination of anabolic agents. Since, PTH is the only approved bone anabolic drug, but with serious side-effects, there is a great need for new bone forming agents like BMP-6. Potential new anabolic treatment could affect a public health problem and Croatia could participate in the benefits of a global drug market for osteoporosis.
1. Simic P et al. J Biol Chem 2006; 281: 25509-21
Target groups:
To our knowledge an estimated 75 million people have osteoporosis and global market is worth 5.6 bn € with a forecast to grow to 10.5 bn € by 2011 with predomination of anabolic agents. Since, PTH is the only approved bone anabolic drug, but with serious side-effects, there is a great need for new bone forming agents like BMP-6. Potential new anabolic treatment could affect a public health problem and Croatia could participate in the benefits of a global drug market for osteoporosis.
1. Simic P et al. J Biol Chem 2006; 281: 25509-21