Findings of a recent international study involving WA researchers point to the potential application of mitochondrial therapy for some bone-related diseases. The study published in the scientific journal Nature Communications has delivered new insights on the interactions between osteocytes as bone formation regulators and transcortical vessels (TCVs) that are a crucial part of the vascular system for bone and bone marrow homeostasis.
The results were exciting because they have opened the possibility of a molecular therapeutic approach for bone diseases associated with vascular damage. As well as providing the body’s structural support, skeletal bones host blood stem cells (hematopoietic cells) which regulate the body’s immunological system and blood cell production.
Blood vessels are widely distributed in bone and this vascular network plays a critical role in controlling bone development and wound healing. The network also provides a microenvironment for the differentiation and maturation of hematopoietic and immune cells in bone marrow. The link between blood diseases and skeletal health has been well documented, for example, the association between anaemia in older populations and bone fragility.
Inside the hard shell of skeletal bone tissue, blood production cells, including immune cells, erythrocytes, platelets and leukocytes require an extensive vascular network to migrate rapidly from the bone marrow and reach the general circulation in responding to various physiological and pathological conditions.
To achieve this, there is a highly vascularised periosteum (outer layer) around the hard shell of bone also connected to the general circulation of the body. Recently it has been discovered that there are TCVs across the hard shell of bone enabling the connection of bone marrow to the periosteum.
While TCVs provide effective communication between the bone marrow vascular system and external circulation, it has not been clear how these TCVs are maintained and regulated in the body.
This study revealed a crucial role of osteocytes in TCV vascularisation, showing that these cells maintain a normal TCV network by transferring mitochondria to endothelial cells in cortical bone. The research showed for the first time that osteocytes in cortical bone stretch their dendrites with endfeet-like structures to endothelial cells and directly communicate with the TCVs’ network.
The acquisition of osteocyte mitochondria by endothelial cells maintains normal functions by alleviating oxidative stress, promoting cell proliferation, advancing tube formation and restoring the migration capability of endothelial cells. It efficiently restores endothelial dysfunction, accelerating blood vessel formation and healing of the cortical bone defect.
In contrast, the study found that partial ablation of osteocytes causes TCV regression. Blood vessels widely distributed in bone are necessary for bone and bone marrow homeostasis – the set of interactions that result in overall maintenance of bone mass.
The results of this study are important because they provide new insights into this vascular system and its cellular interactions within bone and bone marrow. A crucial role of osteocytes in the regulation of vascularisation in bone tissue has been identified. They inspire the potential application of mitochondrial therapy for bone-related diseases.
Key messages
- New research suggests a potential for mitochondrial therapy in some bone diseases
- Cellular interactions within bone and bone marrow and this vascular system were found
- A crucial role of osteocytes in the regulation of vascularisation in bone tissue was found.
– References available on request
Author competing interests- the author was involved in the study described