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Bone Metabolism
Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called ''bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). These processes also control the reshaping or replacement of bone following injuries like fractures but also micro-damage, which occurs during normal activity. Remodeling responds also to functional demands of the mechanical loading. In the first year of life, almost 100% of the skeleton is replaced. In adults, remodeling proceeds at about 10% per year. An imbalance in the regulation of bone remodeling's two sub-processes, bone resorption and bone formation, results in many metabolic bone diseases, such as osteoporosis. Physiology Bone homeostasis involves multiple but coordinated cellular and molecular events. Two main types of cells are responsible for bone metabolism: osteoblasts (which secrete new bone), and osteoclasts (which brea ...
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Calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH). Its importance in humans has not been as well established as its importance in other animals, as its function is usually not significant in the regulation of normal calcium homeostasis. It belongs to the calcitonin-like protein family. Historically calcitonin has also been called thyrocalcitonin. Biosynthesis and regulation Calcitonin is formed by the proteolytic cleavage of a larger prepropeptide, which is the product of the CALC1 gene (). It is functionally an antagonist with PTH and Vitamin D3. The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor protein, calcitonin gene-related peptide, and the precursor of adrenomedullin. Secretion of ...
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Wolff's Law
Wolff's law, developed by the German anatomist and surgeon Julius Wolff (surgeon), Julius Wolff (1836–1902) in the 19th century, states that bone in a healthy animal will adapt to the loads under which it is placed. If loading on a particular bone increases, the bone will remodel itself over time to become stronger to resist that sort of loading. The internal architecture of the trabeculae undergoes adaptive changes, followed by secondary changes to the external cortical portion of the bone, perhaps becoming thicker as a result. The inverse is true as well: if the loading on a bone decreases, the bone will become less dense and weaker due to the lack of the stimulus required for continued bone remodeling, remodeling.Wolff J. "The Law of Bone Remodeling". Berlin Heidelberg New York: Springer, 1986 (translation of the German 1892 edition) This reduction in bone density (osteopenia) is known as stress shielding and can occur as a result of a hip replacement (or other prosthesis). ...
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Tissue Remodeling
Tissue remodeling is the reorganization or renovation of existing tissues. Tissue remodeling can be either physiological or pathological. The process can either change the characteristics of a tissue such as in blood vessel remodeling, or result in the dynamic equilibrium of a tissue such as in bone remodeling. Macrophages repair wounds and remodel tissue by producing extracellular matrix and proteases to modify that specific matrix. A myocardial infarction induces tissue remodeling of the heart in a three-phase process: inflammation, proliferation, and maturation. Inflammation is characterized by massive necrosis in the infarcted area. Inflammatory cells clear the dead cells. In the proliferation phase, inflammatory cells die by apoptosis, being replaced by myofibroblasts which produce large amounts of collagen. In the maturation phase, myofibroblast numbers are reduced by apoptosis, allowing for infiltration by endothelial cells (for blood vessels) and cardiomyocytes (heart tissu ...
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Osteocyte
An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active osteoblasts (which may further differentiate to osteocytes). Osteoblasts/osteocytes develop in mesenchyme. In mature bones, osteocytes and their processes reside inside spaces called lacunae (Latin for a ''pit'') and canaliculi, respectively. Osteocytes are simply osteoblasts trapped in the matrix that they secrete. They are networked to each other via long cytoplasmic extensions that occupy tiny canals called canaliculi, which are used for exchange of nutrients and waste through gap junctions. Although osteocytes have reduced synthetic activity and (like osteoblasts) are not capable of mitotic division, they are a ...
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Osteoid
In histology, osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins. When the osteoid becomes mineralized, it and the adjacent bone cells have developed into new bone tissue. Osteoid makes up about fifty percent of bone volume and forty percent of bone weight. It is composed of fibers and ground substance. The predominant type of fiber is type I collagen and comprises ninety percent of the osteoid. The ground substance is mostly made up of chondroitin sulfate and osteocalcin. Disorders When there is insufficient nutrient minerals or osteoblast dysfunction, the osteoid does not mineralize properly, and it accumulates. The resultant disorder is termed rickets in children and osteomalacia in adults. A deficiency of type I collagen, such as in osteogenesis imperfecta, also leads to defective osteoid and brittle, f ...
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Bone Remodeling Period
In bone physiology, the bone remodeling period describes the temporal duration (i.e. lifespan) of the basic multicellular unit (BMU) that is responsible for bone turnover. Historically, this was referred to as the sigma (σ) or sigma period, but the terminology is now outdated. Bone remodeling Although bone may appear superficially as a static tissue, it is actually very dynamic, undergoing constant remodeling throughout the life of the vertebrate organism. This occurs with the synchronized action of osteoclasts and osteoblasts, cells that resorb and deposit bone, respectively. The remodeling period The remodeling period consists of the combined duration of the resorption, the osteoclastic reversal (the phase marked by shifting of resorption processes into formative processes) and the formation periods of bone growth and development. This period refers to the average total duration of a single cycle of bone remodeling Bone remodeling (or bone metabolism) is a lifelong pro ...
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Interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1 and its activation of IL-1ra and IL-10. There is some early evidence that IL-6 can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis, in the context of the wider coronavirus pandemic. Function Immune system IL-6 is secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns ( PAMPs). These PAMPs bind to an important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), incl ...
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VEGF
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis (the '' de novo'' formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions. Serum concentration of VEGF is high in bronchial asthma and diabetes mellitus. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. It can contribute to disease. Sol ...
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RANKL
Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the ''TNFSF11'' gene. RANKL is known as a type II membrane protein and is a member of the tumor necrosis factor (TNF) superfamily. RANKL has been identified to affect the immune system and control bone regeneration and remodeling. RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls cell proliferation by modifying protein levels of Id4, Id2 and cyclin D1. RANKL is expressed in several tissues and organs including: skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas. Variation in concentration levels of RANKL throughout sever ...
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M-CSF
The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta. Structure M-CSF is a cytokine, being a smaller protein involved in cell signaling. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein) have been found for this gene. Function M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the prol ...
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Growth Factors
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes. Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells. They often promote cell differentiation and maturation, which varies between growth factors. For example, epidermal growth factor (EGF) enhances osteogenic differentiation, while fibroblast growth factors and vascular endothelial growth factors stimulate blood vessel differentiation (angiogenesis). Comparison to cytokines ''Growth factor'' is sometimes used interchangeably among scientists with the term ''cytokine.'' Historically, cytokines were associated with hematopoietic (blood and lymph forming) cells and immune syst ...
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