Anatomy, physiology and disease
C M Langton, C F Njeh in The Physical Measurement of Bone, 2016
In general, there are three specific ‘programmes’ which are followed by the osteoblast over its life span: proliferation, differentiation, and mineralization. As noted in figure 1.1, the interaction of all three components of bone is best exemplified by the life cycle of the osteoblast. After originating from stem cells, osteoblasts are committed towards a specific bone phenotype by both transcription factors and growth factors, some of which are tissue specific, such as bone morphogenic protein-2 and Cbfa1, and others which are non-specific such as c-fos, and egr [24–29]. The expression of bone-specific markers in osteoblasts is time-specific. After a period of proliferation, which is accelerated by several growth factors including the insulin-like growth factors (IGFs), transforming growth factor-beta, fibroblast growth factor and the bone morphogenic proteins (BMPs), differentiative markers are expressed [30–35]. These include alkaline phosphatase and bone sialoprotein as early indices. Later on, as osteoblasts line the bone surface (figure 1.2) osteopontin and osteocalcin are released. In vitro, mature osteoblasts can form nodules and begin the process of mineralization. Osteoblasts are also thought to regulate the local concentrations of calcium and phosphate in such a way as to promote the formation of an apatite matrix. The production of heteropolymeric matrix fibrils from collagen synthesized by osteoblasts is likely to be a key step prior to mineralization, although the precise mechanism is not well delineated (see section 1.5).
The locomotor system
C. Simon Herrington in Muir's Textbook of Pathology, 2020
The protein matrix of bone consists largely of type I collagen produced by osteoblasts. There are, in addition, small amounts of non-collagenous proteins including calcium-binding proteins such as osteonectin and bone sialoprotein and those involved in mineralization such as osteocalcin. Cell adhesion proteins, including osteopontin and growth factors including transforming growth factor (TGF), are also present.
Osteoporosis
Peter V. Giannoudis, Thomas A. Einhorn in Surgical and Medical Treatment of Osteoporosis, 2020
Bone sialoprotein (BSP) is a phosphorylated glycoprotein that accounts for up to 10% of the noncollagenous proteins of the bone matrix. It is the product of osteoblasts and odontoblasts; hence, it is relatively limited to mineralized tissues. It is believed to be an adhesion molecule of cells to the extracellular matrix and facilitates the organization of the extracellular matrix.
Green nanotechnology-based drug delivery systems for osteogenic disorders
Published in Expert Opinion on Drug Delivery, 2020
David Medina-Cruz, Ebrahim Mostafavi, Ada Vernet-Crua, Junjiang Cheng, Veer Shah, Jorge Luis Cholula-Diaz, Gregory Guisbiers, Juan Tao, José Miguel García-Martín, Thomas J. Webster
Oligopeptides are small sequences of amino acids, naturally present in the human body, which have the ability to link to HA when aspartic acid (Asp) and glutamic acid (Glu) residues are present in their structure, preventing bone resorption [32,33]. Osteopontin and bone sialoprotein are two major noncollagenous proteins in bone, which have both L-Asp and L-Glu repetitive sequences in their structure, respectively, aiding the process of rapid binding to HA once secreted in osteoblastic cell culture. Thus, these oligopeptides are suitable candidates as bone-targeting agents that can be combined with different drugs (Figure 1(b)). For instance, after systemic administration, a drug tagged with an oligopeptide can be selectively delivered to bind with bone, acting as the active drug which is gradually released during the bone remodeling process [34–36].
Understanding collagen interactions and their targeted regulation by novel drugs
Published in Expert Opinion on Drug Discovery, 2021
Marialucia Gallorini, Simone Carradori
Vitronectin (VN) is a multifunctional glycoprotein which binds to different biological ligands and, by binding to different types of integrins, mostly via the RGD sequence, plays a key role in tissue remodeling by controlling cell adhesion. In addition to that, VN owns two domains for collagen-binding and interacts with collagens I, II, III, IV, V and VI. As for fibronectin (FN), its interactions with collagen are crucial during the genesis of fibrils. Fibronectin has also been discovered as a target protein for the diagnosis of high-risk micro-metastasis of breast cancer. A successful approach to prevent metastatic invasion could be the selective delivery of therapeutic drugs to highly fibronectin-expressing metastatic tumor sites [93]. Finally, the crosstalk between collagens and non-collagenous bone proteins, such as bone sialoprotein II (BSPII) and osteonectin (SPARC, secreted protein acidic and rich in cysteine), is involved in tissue remodeling and cancer-related metastases. The SPARC protein has furthermore been identified as a potential therapeutic target to prevent breast cancer bone metastasis [94].
Therapeutic potential of RUNX1 and RUNX2 in bone metastasis of breast cancer
Published in Expert Opinion on Therapeutic Targets, 2023
The ‘seed and soil’ doctrine was proposed in 1889, where the cancer cell was the seed and the bone was the soil, stating that metastatic colonization of distal organs was not a random process and that cancer cells could only grow in a microenvironment that was conducive to their growth. This theory was confirmed in 2015 by the fact that tumor metastasis was not random but rather directed [31]. Through the presence of integrins on the exosomal membrane, breast cancer cells modify the bone microenvironment. This allows cancer cells to adapt to the new microenvironment and interact with skeletal resident cells (osteoblasts, osteocytes, and osteoclasts) and other cells in the bone marrow. In the vicious cycle of bone metastasis, osteoclasts are activated either directly or indirectly by tumor cells. RUNX2 and CBF-β regulate cancer-related genes, such as osteocalcin, bone sialoprotein, matrix metalloprotein 9 (MMP9), and matrix metalloprotein 13 (MMP13) [32]. This may increase osteoclast function, leading to pathological bone resorption and a vicious cycle of bone metastasis. Osteolytic, osteoblastic, and mixed are the three categories of bone metastases.
Related Knowledge Centers
- Bone
- Cartilage
- Complementary DNA
- Dentin
- Sialic Acid
- Cementum
- Mineralized Tissues
- Sibling Proteins
- Gene
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