Early 2017 I got funding to start assembling an independent research group working on regulation of bone remodeling and development of in vitro model to replicate the bone remodeling cycle. Later the same year a starting grant from Swedish Research Council allowed for its expansion. I did my PhD at University of Turku in Finland. Then I moved to Department Neurosciences at Karolinska institutet for a postdoc project on regulation synaptic vesicle membrane trafficking. After that I joined Division of Pathology in Department of Laboratory Medicine for another postdoc to study differentiation of osteoclasts.
We will develop an in vitro model recreating the entire bone remodeling cycle to examine in detail processes regulating bone remodeling and bone generation. My group’s long-term aim is to screen better small molecule drugs for osteoporosis and to produce bone for regenerative medicine. Bone remodeling is a constantly undergoing process where bone resorbing osteoclasts (OC), osteocytes (OY) inhabiting channels inside bone and bone mineralizing osteoblasts (OB) work together in order to heal damage and remake the skeleton, respond to mechanical stimulus and adapt bone structure to environmental factors and maintain Ca2+ and phosphate homeostasis. These cells receive regulatory signals through hormonal signaling network and transmit information to each other directly with cell-cell contacts, with soluble ligands as well as through surrounding extracellular matrix. I have developed an in vitro model of bone composed of sedimented bone nanoparticles facilitating easy high-resolution imaging to extract molecular detail in a relevant biological context. The primary aims of the proposed project are to:
1. further develop this model to include OYs, OCs, and OBs, and functionalization (e.g. proteins NO and pH-probes).
2. Elucidate and understand the coupling mechanisms in the intertwined signaling between OCs, OBs and OYs in mineralization. While OYs stimulate differentiation of OCs and OBs they also inhibit it by osteoprotegerin and sclerostin, respectively. In our model we can examine the impact of the signals in a sub-cellular resolution enabling us to establish precise molecular mechanisms.
3. Learn how to modulate balance between mineralization and resorption in an in vitro model replicating the bone-remodeling unit and to screen for drug candidates affecting the balance of the bone remodeling cycle.
Laia Mira Pascual (PhD-student shared with G. Andersson and P. Lång)
Students wishing to do their M.Sc. thesis work in the group are welcome to contact firstname.lastname@example.org
Academic honours, awards and prizes
Jane and Aatos Erkko foundation
Loo and Hans Osterman foundation
Maud Kuistila memorial foundation