New cell type promoting osteogenesis in bone
Processes and Methods (incl. Screening) : Life Sciences-HTS/HCS
Nucleic Acid-, Protein and Cell-related Technologies : Cell related
The mammalian skeletal system harbors a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in the ageing organism, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanism.
In addition to well-known differences between arteries, capillaries and veins, endothelial cells (ECs) are highly heterogeneous and acquire specialized functional properties in local microenvironments. Scientist from the team of Prof. Ralf Adams at the Max Planck Institute for Molecular Biomedicine have identified a new subtype of capillary ECs in the murine skeletal system with distinct morphological, molecular and functional properties. These ECs, termed type H, were shown to mediate growth of the bone vasculature and promote osteogenesis. Type H ECs, which are located in the metaphysis and endosteum of long bone, are distinguishable by expression of the cell surface markers CD31 (also known as PECAM1) and Endomucin (Emcn). In contrast to these rare CD31hi Emcnhi ECs, the vast majority of the bone endothelium (termed CD31lo Emcnlo or type L) displays low abundance of CD31 and Emcn, is found within the diaphysis and is not associated with osteoprogenitors.
At the molecular level, endothelial hypoxia-inducible factor (HIF) and Notch signaling control the abundance of type H ECs, increase the number of vessel-associated osteoprogenitor cells and enhance bone formation. During ageing, which is associated with a reduction of osteoprogenitors and the loss of bone mass, the fraction of type H vessels declines strongly whereas the total number of bone ECs remains unchanged. Importantly, induction of type H vessels via reactivation of endothelial HIF or Notch signaling in ECs was sufficient to increase osteoprogenitors and improve bone quality in aged mice.
The abundance of type H cells may be useful as diagnostic read-out for the status of the bone vasculature and its pro-osteogenic capacity. Furthermore, increase of type H cells might offer a novel therapeutical strategy for the prevention of bone loss and improved fracture healing in elderly people.
In summary, Prof. Adams and his colleagues have identified a new capillary subtype in the murine skeletal system, which is found in specific locations, mediates growth of the bone vasculature, generates distinct metabolic and molecular microenvironments, maintains perivascular osteoprogenitors, and couples angiogenesis to osteogenesis.
We are looking for a licensing partner that is interested in this technology. We will be pleased to share detailed information and scientific data.
International patent application: PCT/EP14/072069.
- Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Anjali P.Kusumbe, Saravana K. Ramasamy, Ralf H. Adams. Nature 2014, Mar 20:507(7492):323-8.
- Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Ramasamy SK, Kusumbe AP, Wang L, Adams RH. Nature 2014 Mar 20:507(7492):376-80.
- Ref.-No.: 1012-4727-IKF (143.2 KiB)
Dr. Ingrid Kapser-Fischer
Phone: +49 89 / 29 09 19-19