The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis

Abstract

Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form “type H” capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling.

Type H blood vessels in coupling angiogenesis‐osteogenesis and its application in bone tissue engineering

“…The oxygen content in the vasculature of the skeletal system is consistent with blood flow pattern. Because of being directly connected to the arterioles, type H vessels have higher oxygen concentration, 30 which meets the energy demands in the metaphyseal region for trabecular bone formation 31 …”

“…Because of being directly connected to the arterioles, type H vessels have higher oxygen concentration, 30 which meets the energy demands in the metaphyseal region for trabecular bone formation. 31 Evidence shows that blood flow is also closely related to the generation of type H vessels. Reducing blood flow by femoral artery ligation or admitting flow-reducing drug (Prazosin or Clonidine) both led to a significant reduction of the bundance of vascular buds near the growth plate and the number of type H vessels in the epiphysis.…”

Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia

“…Osteoblasts synthesize almost all constituents of the bone matrix and regulate bone mineralization [ 7 ]. Toll-like receptor 4 (TLR4) is expressed by osteoblasts and is thereby a regulator of bone formation [ 8 ].…”

Covalent immobilization of VEGF on allogeneic bone through polydopamine coating to improve bone regeneration

“…Bone is a kind of tissue with a high potential for regeneration, and therefore most fractures or bone abnormalities can repair themselves following stable fixation ( Neag et al, 2021 ). Mechanical stress, biochemical mediators, bioelectric and piezoelectric qualities, and neurological and endocrine impacts all influence the bone healing process ( Mann and Payne, 1989 ).…”