The skeletal system supports the body shape and helps in movement. Skeletons are a dynamic tissue, constantly rebuild and reabsorb throughout lifetime (Karsenty and Wagner, 2002). Bone formation (osteogenesis), growth and remodeling are highly dependent on new blood vessel formations (angiogenesis) (Brandi and Collin-Osdoby, 2006). Notably, angiogenesis plays a major role in fracture healing and repair. Moreover imbalance of the vasculature leads to progression of numerous bone diseases (osteoporosis, osteonecrosis, rheumatoid arthritis, bone cancer and metastasis)(Carulli et al., 2013). In angiogenesis, avascular region of the tissue is hypoxic and secretes angiogenic factors to induce the new blood vessel formation form existing ones (Potente et al., 2011). The inner layer of blood vessel is covered by endothelial cells (ECs) and shielded by perivascular cells (pericytes and smooth muscle cells) and outer layer is directly connected to the vascular beads (Carmeliet and Jain, 2011). Further, the vessel formation, architecture and function are varying in organ specific manner (Rocha and Adams, 2009). Signal from perivascular …show more content…
Proper communications between these processes are essential for bone development, growth and homeostasis. Bone angiogenesis is a key player in these processes. Bone cells secrete angiogenic factor (e.g, Vegfa, Fgf and Tgf) to induce bone angiogenesis and angiocrine signal stimulate chondrogenesis and osteogenesis (Gerber and Ferrara, 2000). Additionally, vascular system supports hematopoiesis through its niche signal. This signal act as an extrinsic signal to control hematopoietic stem cell (HSC) maintenance and differentiation (Ugarte and Forsberg, 2013). Blood vessels are important and plays vital role in bone. In this review we focus on bone vasculature architecture and formation, and its role in osteogenesis, pathological settings like fracture healing and
An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.
Compact bone looks dense and solid, yet it is filled with passageways that serve as conduits for nerves, blood vessels, and lymphatic vessels (Marieb, 181).
Blood supply to the nutrient arteries of a long bone occur through the nutrient foramina, the nutrient foramina aids in the growth and nutrition of bones. (Vinay and Arun, 2011).
Michael Longaker’s interests lie at the intersection of wound/bone regeneration and stem cell biology. In the Peripheral Blood-Derived Mesenchymal Stem Cells: Candidate Cells Responsible for Healing Critical-Sized Calvarial Bone Defects, the efficacy of peripheral blood (PB) for use in regenerative medicine is significant, with its retrieval viewed as relatively easy. Experiments such as bone regeneration were carried out with the use of PB stem cells. The paper finds that through a specific coculturing process mesenchymal cells can be derived from PB (CD34+) which happen to be choice candidates for quicker bone healing and re-calcification in bone defects (Li). The key discoveries here are the identification of easily retrievable source of stem cells, which help give rise, under a specific culturing protocol, to a specific group of non-hematopoietic cells. This is directly in line with Dr. Longaker’s research as he investigates the possible uses of regenerative medicine in skeletal regeneration. Here we are provided an example of how these CD45- cells can be utilized for treatment of bone defects as it facilitations bone formation and osteogenesis. What should be asked here is how viable is this form of treatment. There is a lot of discussion surrounding the necessary conditions to produce these BD-MSCs and how it is very condition dependent. It would have been preferable to know the amount of time and the amount of cells required to see efficient
Longitudinal bone growth occurs at the epiphyseal plate, which is a thin layer of cartilage between the epiphyseal and metaphyseal bone at the distal ends of the long bones. Bone growth is the result of maturation, growth of chondrocytes, their production of bone matrix, and finally calcification (47). The growth plate is a complex structure consisting of different layers of cells, as shown in figure 3. The most immature cells, the stem cells, are found towards the epiphyseal end of the growth plate in the stem cell zone, or resting zone; the proliferating zone contains more mature chondrocytes and the hypertrophic zone contains the larger chondrocytes. The resting stem cells in the resting zone are recruited, whereupon proliferation and differentiation
Haematopoietic stem cells (HSC) regulate the turnover of platelets, erythrocytes and all immune cells by changing between self-renewal and differentiation to a variety of specialised cells. Osteoblasts has a major role of secretion of mineralized bone matrix proteins and cells of the osteoblast lineage regulating osteoclast differentiation. (Purton & Scadden, 2008)
Bone is surrounded by a thin membranous layer of soft tissue called periosteum (Singh, 2017). When the bone breaks it bleeds from torn ends because of the disruption of the supplying blood vessels. And quite naturally the periosteum is also torn. A fracture hematoma forms and white blood cells march in to clean up the area that is injured. The periosteum is the primary source of osteoblasts, which plays a huge role in fracture healing (Singh, 2017). After the hematoma formation, the next step is callous formation with the formation of cartilage and bone and then the remodeling phase consisting of the osteoclasts and the osteoblasts reshaping the bone to its original state (Patton, 2012).
Osteopontin (OPN), an acidic bone-forming protein is widely present in human tissues and is secreted or synthesized by a wide variety of cell types including vascular cells. It has different physiological and pathological functions like cell migration, adhesion, and survival in many cell types [110-111]. This bone-matrix protein is also localized at inflammatory sites [112] to reduce inflammation and is involved in tissue remodeling [113] as well as modulation of VC [114-115] through reducing growth and formation of calcium crystals by binding hydroxyapatite and calcium ions [116]. OPN is also directly associated with conditions of injury and disease like atherosclerotic lesions [115, 117] containing calcium deposits [118] and coronary artery
The growth plates are a cartilaginous tissue found at the distal ends of the long bones between the metaphyseal and epiphyseal bone (Fig 1). They consist of three principal zones of chondrocytes: the resting zone, the proliferative zone and the hypertrophic zone, where the hypertrophic chondrocytes are the most differentiated (Fig 1) (16,17). Longitudinal bone growth of the long bones occurs at the growth plates through a process called endochondral ossification. In this process the chondrocytes proliferate, become more differentiated and finally become hypertrophic. The hypertrophic chondrocytes enlarge and secrete matrix proteins which form a scaffold for the formation of bone tissue (18). Terminal hypertrophic chondrocytes undergo apoptosis
Osteoblastogenesis takes place as a result of a number of signalling pathways such as the transforming growth factor-β (TGF-β), Wnt/β-catenin and mitrogen-activated protein kinase (MAPK) signalling. The TGF-β superfamily comprises of the TGF-βs and the bone morphogenetic proteins (BMPs), both of which play critical regulatory roles in bone tissue55,56. TGF-β presents in 3 isoforms namely TGF-β1, TGF-β2 and TGF-β3 with TGF-β1 in particular having a chemotactic effect on osteoblasts in order to promote bone formation55. TGF-β is initially expressed as an inactive complex which is made functional via one of three mechanisms: bond breaking between TGF-β and the latency associated peptide, degradation of the latency associated peptide or conformational change of the latency associated peptide itself55. Post-activation, the TGF-β binds to either type I or type II of the transmembrane serine/threonine receptors57.
The bone marrow is layers of tissue found inside bones, made up of specialised cells called megakaryocytes which have the responsibility of producing thrombocytes(platelet) (6). The main role of platelets is the formation of blood clots to prevent excessive bleeding which can have dangerous complexities on health. Thrombocytes work on a specific layer called the endothelium made up of simple, squamas cells called endothelial cells. The function of the endothelium is to act as a semi-permeable barrier, assist in vasoconstriction/dilation and help in thrombosis. When this layer is damaged, blood can rapidly escape, in that case platelets form bonds with protein fibres. By binding together, it blocks the space for blood to escape out of the blood
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels. This is distinct from vasculogenesis, which is the de novo formation of endothelial cells from mesoderm cell precursors. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue40. However, it is also a fundamental step in the transition of tumors from a benign state to a malignant one, leading to the use of angiogenesis inhibitors in the treatment of cancer. The essential
Bone is an active organ in which the organizational distribution of the mineral and organic content determines the successful mechanical function of the skeleton. Bone turnover is controlled by certain agents and mechanisms that adjust bone formation and bone resorption, which are the two main processes of bone remodeling. Disturbances in these mechanisms may lead to either bone loss, resulting in osteoporosis, or an overgrowth of bone, leading to osteosclerosis (1).
Regeneration has been defined as the reproduction or reconstitution of a lost or injured part to restore the architecture and function of the periodontium. To be considered a regenerative modality, a material or technique must histologically demonstrate that bone, cementum and a functional periodontal ligament (a new attachment apparatus) can be formed on a previously diseased root surface. Bone grafts and their synthetic substitutes have been used in an attempt to gain this therapeutic endpoint. However, among the graft materials to date, only autogenous bone of extraoral or intraoral sources and demineralized freeze dried bone allograft have human histological evidence to include them as regenerative materials. More recently the use of recombinant human bone morphogenetic proteins (BMP)-2 (Ishikawa et al. 1994), enamel matrix derivative (EMD) (Sculean et al. 1999), platelet-rich plasma (PRP) (Anitua et al. 2004), growth factors like platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) (Lynch et al. 1989) and recombinant human basic fibroblast growth factor (bFGF) (Murakami et al. 2003) have been proposed as a source for periodontal regeneration. Initial investigation has demonstrated that anorganic bovine bone matrix supports the attachment and proliferation of osteoblastic cells in vitro (Stephan et al. 1999). Indeed, human histologic studies have concluded that this bone substitute is osteoconductive and incorporated in new bone
Currently, there is a global increase in cases of bone disorders and conditions, which is expected to increase as twice as much by 2020 particularly in countries where obesity and poor physical activity are associated with aging[1]. Although reconstructive orthopaedic surgery can be used to treat bone defects and injuries caused by trauma, additional treatments are required for severe breaks or pathological conditions as well as critical bone defects due to malformation, cancer or osteoporosis in order to effectively stimulate healing and regeneration. While traditional autologous and allogeneic bone grafting is ineffective for treating large injuries because of lack of graft vascularization, low cell viability in the host, and other