New cell type promoting osteogenesis in bone

The mammalian skeletal system harbors a hierarchical system of skeletal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation [1, 2]. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in the aging organism. Loss of bone mass and increased fracture incidence are features of osteoporosis, which affects more than 25 million patients in the EU [3] and generates annual costs estimated around 37 billion Euros [3].

Researchers from the Max Planck Institute for Molecular Biomedicine, Prof. Adams and his team, have identified a new subtype of capillary endothelial cells (ECs) in the murine skeletal system with distinct morphological, molecular and functional properties [4, 5]. These ECs, termed type H, were shown to mediate growth of the bone vasculature and promote osteogenesis by releasing signals acting on perivascular osteoprogenitor cells [4, 5, 6]. 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) [5]. There is strong evidence for the existence of type H ECs in the human skeletal system and the decline of these cells is a biomarker for bone loss during aging and in patients with osteoporosis [7].

It is now firmly established that blood vessels in bone and osteogenesis are coupled [6, 8, 9]. At the molecular level, endothelial hypoxia-inducible factor (HIF), Notch signaling and the Hippo pathway control the abundance of type H ECs, increase the number of vessel-associated osteoprogenitor cells and enhance bone formation [4, 5, 6]. Proof-of-principle experiments in animal models have established that genetic or pharmacological approaches leading to the reactivation of endothelial HIF or Notch signaling in ECs induce type H vessels, increase osteoprogenitor cells and improve bone quality in aged mice [4, 5, 6].

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.

Thus, the work by Prof. Adams and his team indicates that capillary ECs may be a promising target to develop treatment options for osteoporosis and other disease conditions associated with bone loss. Further, 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.

We are looking for a licensing partner that is interested in this technology. We will be pleased to share detailed information and scientific data.

A priority establishing patent application has been filed in 2013. There are certain patent rights covering this technology (Title: Reprogramming Bone Endothelial Cells for Use in Bone Angiogenesis and Osteogenesis): US10053668B2 and EP3039125B1 (publication numbers).

[1] Watson EC and Adams RH Cold Spring Harbor Perspectives in Medicine (2018) 8(7): a031559

[2] Ramasamy SK et al., Annual Review of Cell and Developmental Biology (2016) 32:649-675

[3] Hernlund E et al., Archives of Osteoporosis (2013) 8(1):136

[4] Ramasamy SK et al. Nature (2014) 507:376-380

[5] Kusumbe AP et al. Nature (2014) 507:323-328

[6] Sivaraj KK et al., Elife (2020) 9:e50770

[7] Wang L et al. Cell Death & Disease (2017) 8(5):e2760

[8] Langen UH et al. Nature Cell Biology (2017) 19:189-201

[9] Ramasamy SK et al. Nature Communications (2016) 7:13601