A team of researchers from USP’s Chemistry Institute (IQ), USP’s Faculty of Medical Sciences (FMUSP), and other institutions has tested, for the first time, the effectiveness of a combined treatment of two recombinant proteins against osteoporosis in an animal model. Treatment with the BMP-7 and PDGF-BB proteins was performed on rats that had their ovaries removed and developed obesity and osteoporosis. The study’s results showed significant increases in bone volume and density in the rats, indicating a partial reversal of osteoporosis. The discovery could be the key to new therapeutic options against bone degeneration – which will still need to be proven in future clinical studies.
Osteoporosis is a disease that affects approximately 200 million people worldwide, with a higher prevalence in post-menopausal women and the elderly. It is characterized by loss of mass and degeneration of bone tissue, which can lead to a greater risk of fractures and, consequently, more significant morbidity and mortality in this population. Because of this, exploring new treatment options is necessary to ensure a better quality of life and longevity for those affected by the condition.
Today, the therapies available on the market are divided into two categories: anti-bone resorption drugs and anabolic drugs, which stimulate bone formation. In healthy bone tissue, there is a balance between bone destruction and reconstruction processes, ensuring the absorption of essential compounds for the body, such as calcium, and replacing old structures with newer ones. In people with osteoporosis, however, the imbalance between these two activities causes more tissue to be degraded – or reabsorbed – and the cells cannot replenish this bone mass in the same proportion.
In this context, anti-resorption drugs prevent tissue from being naturally destroyed; however, they don’t solve the problem of replacement. Therapies that stimulate bone formation, on the other hand, are effectively capable of reversing osteoporosis. This type of drug, already on the market, however, tends to cause many adverse effects in patients – the most important being an increased risk of cardiovascular disease, gastrointestinal problems, and reductions in bone volume after discontinuation of use.
Treatment with BMP-7 and PDGF-BB, which also affect bone mass formation, has proved to be a potential alternative to current commercial drugs.
Combined proteins
BMP-7 and PDGF-BB belong to a class of molecules called Peptide Growth Factors, which play important roles in embryonic development and bone regeneration and formation. The BMP family (Bone Morphogenetic Proteins) is responsible for regulating and balancing bone tissue, cartilage repair, embryonic development, cell proliferation, and differentiation, among other known functions. In the specific case of BMP-7, it is known to induce the differentiation of stem cells into cell lineages that give rise to bone (osteocytes). The family of PDGFs (Platelet-Derived Growth Factors) performs a chemical signaling function in tissues, playing an essential role in their healing. PDGF-BB, in particular, plays a crucial role in the repair of skin and other soft tissues, as well as bone fractures, as it regulates which cells and molecules should be recruited to restore damaged tissue.
Because of these well-known and well-described properties in the literature, the two proteins were chosen for the study published in the scientific journal Biomolecules. According to Mari Cleide Sogayar, senior lecturer at IQ and corresponding author of the article, “these proteins act at the level of their receptors, which are located on the cell membrane. When they bind to their receptor, this triggers a signaling cascade that reaches the nucleus, where gene transcription takes place”. In other words, this cascade represents a sequence of biochemical reactions that tell the cell what to do, in this case, to produce new bone.
After selecting and synthesizing these two recombinant proteins, generically known as biopharmaceuticals, the researchers artificially induced osteoporosis in female rats by removing their ovaries. Different protein administration protocols were then designed. The trial involved the joint and individual application of the two molecules at different doses and time intervals. In the end, it was found that the joint treatment of BMP-7 and PDGF-BB effectively increased bone volume and density in this animal model.
Biopharmaceutical research
Professor Mari Cleide Sogayar’s laboratory, currently based at FMUSP, is one of the few in Brazil dedicated to producing and researching biopharmaceuticals – that is, recombinant proteins artificially synthesized in cell cultures with biological properties and therapeutic applications. According to her, this area is still little explored in the country, but it is also very important in the national context. “Here, we produce molecules to treat hemophilia, hormones used in assisted reproduction, and even biopharmaceuticals to control diabetes,” she says.
The group does research with them and partners with companies to develop commercial products and obtain patents, aiming at regenerative medicine. For the researchers, biopharmaceuticals represent a revolution in science and health and deserve greater attention from the population and national authorities.
The article Recombinant Human Peptide Growth Factors, Bone Morphogenetic Protein-7 (rhBMP7), and Platelet-Derived Growth Factor-BB (rhPDGF-BB) for Osteoporosis Treatment in an Oophorectomized Rat Model is available at this link.
More information: mcsogayar@gmail.com; mcsoga@iq.usp.br, with Mari Cleide Sogayar.
*By Bruna Larotonda, from IQ's Communications Office. Adapted for Jornal da USP
