300 px, Bone tissue is removed by osteoclasts, and then new bone tissue is formed by osteoblasts. Both processes utilize cytokine ( IGF) signalling.">Insulin-like_growth_factor.html" ;"title="TGF-β, Insulin-like growth factor">IGF) signalling. In osteology, bone remodeling or bone metabolism is a lifelong process where mature osseous tissue, bone tissue is removed from the skeleton (a process called ''bone resorption'') and new bone tissue is formed (a process called ''

ossification Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in t ...

'' or ''new bone formation''). Recent research has identified a specialised subset of blood vessels, termed Type R endothelial cells, in the bone microenvironment. These blood vessels play a crucial role in adult bone remodelling by mediating interactions between bone-resorbing osteoclasts and bone-forming osteoblasts. Type R blood vessels are characterised by their association with post-arterial capillaries and exhibit unique remodelling properties crucial for bone homeostasis. These processes also control the reshaping or replacement of bone following injuries like

fractures Fracture is the appearance of a crack or complete separation of an object or material into two or more pieces under the action of stress (mechanics), stress. The fracture of a solid usually occurs due to the development of certain displacemen ...

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 Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

Physiology

Bone

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

involves multiple but coordinated cellular and molecular events. Two main types of cells are responsible for bone metabolism:

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

s (which secrete new bone), and

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s (which break bone down). The structure of bones as well as adequate supply of

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

requires close cooperation between these two cell types and other cell populations present at the bone remodeling sites (e.g. immune cells). Bone metabolism relies on complex signaling pathways and control mechanisms to achieve proper rates of growth and differentiation. These controls include the action of several hormones, including

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates serum calcium and phosphate through its actions on the bone, kidneys, and small intestine. PTH incre ...

(PTH),

vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

steroids A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter mem ...

, and

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 ...

, as well as several

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

-derived membrane and soluble

cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

and

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 regu ...

(e.g.

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 ...

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 differentiat ...

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 ...

and IL-6 family). It is in this way that the body is able to maintain proper levels of

required for physiological processes. Thus bone remodeling is not just occasional "repair of bone damage" but rather an active, continual process that is always happening in a healthy body. Subsequent to appropriate signaling, osteoclasts move to resorb the surface of the bone, followed by deposition of bone by osteoblasts. Together, the cells that are responsible for bone remodeling are known as the basic multicellular unit (BMU), and the temporal duration (i.e. lifespan) of the BMU is referred to as the

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 t ...

.Pietrzak, WS. Musculoskeletal tissue regeneration: biological materials and methods, Humana Press, 2008. page 48

Gallery

active osteoblasts.jpg, Osteoblasts actively synthesizing

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. The os ...

containing two

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 an ...

s. bone regeneration - Bone remodeling cycle III - Osteoclasts Monocytes Pre-osteoblasts etc -- Smart-Servier (cropped).jpg, Illustration showing bone remodelling cycle osteoclast.jpg, Osteoclast, with bone below it, showing typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.

References

{{bone/cartilage physiology category:animal physiology category:bones

Physiology

Gallery

See also

References