Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells, as well as the osteoclast itself, produce cytokines that can affect osteoclast formation and osteoclast activity.
What stimulates bone remodeling?
The regulation of bone remodeling is both systemic and local. The major systemic regulators include parathyroid hormone (PTH), calcitriol, and other hormones such as growth hormone, glucocorticoids, thyroid hormones, and sex hormones.
How is bone Remodelling regulated?
Bone remodeling is specifically regulated by a crosstalk between bone cells. The process of bone remodeling involves resorption, controlled by osteoclasts, and bone formation, associated with the activity of osteoblasts.
What do macrophages do in bone remodeling?
Macrophages construct a cellular canopy structure over bone remodeling sites, coordinate osteoclast-to-osteoblast coupling, and drive anabolic cytokines for bone formation. Macrophages also create a regenerative microenvironment in the fracture healing processes.
What two factors cause bone remodeling?
Bone growth factors affect the process of bone remodeling. These factors include insulin-like growth factors I and II, transforming growth factor beta, fibroblast growth factor, platelet-derived growth factor, and bone morphogenetic proteins. Bone volume is determined by the rates of bone formation and bone resorption.
What cells are involved in bone remodeling?
- Osteoclasts. Osteoclasts are terminally differentiated myeloid cells that are uniquely adapted to remove mineralized bone matrix.
- Osteoblasts.
- Osteocytes.
- Immune Cells Involved in Physiological Bone Remodeling.
- T-cells and B-cells.
- Megakaryocytes.
- Osteomacs.
What is a cytokine and what does it do?
(SY-toh-kine) A type of protein that is made by certain immune and non-immune cells and has an effect on the immune system. Some cytokines stimulate the immune system and others slow it down. They can also be made in the laboratory and used to help the body fight cancer, infections, and other diseases.
Which cytokines and receptors are negative regulators of osteoclast function?
Interferon regulatory factor (IRF)-8, induced by IFN-γ, is a critical negative regulator for osteoclastogenesis in humans and mice, and its down-regulation by RANKL is essential for osteoclastogenesis [38].
What cytokine induces rankl expression?
The proinflammatory cytokine IL-15 is a strong stimulator of TNF-α, which induces RANKL expression in OBs and stromal cells, resulting in enhanced osteoclastogenesis (53).
What are the 4 stages of bone remodeling?
ACTIVATION, RESORPTION, REVERSAL, FORMATION, and QUIESCENCE. The total process takes about 4 to 8 months, and occurs continually throughout our lives.
What hormones are involved in bone growth?
The female hormone estrogen and the male hormone testosterone both have effects on bone in men and women (Falahati-Nini, Riggs et al. 2000). The estrogen produced in children and early in puberty can increase bone growth.
Which hormone increases osteoclast activity?
Parathyroid hormone (PTH) stimulates osteoclast proliferation and resorption of bone by osteoclasts.
Is osteoblast a macrophage?
Resident tissue macrophages of bone, termed osteal macrophages, are recently classified myeloid cells that are distinct from osteoclasts. Osteal macrophages are located immediately adjacent to osteoblasts, regulate bone formation, and play diverse roles in skeletal homeostasis.
Is osteoclast a macrophage?
The Macrophages Are One of the Origins of Osteoclasts. Osteoclasts are well-defined and distinctive in bone marrow, which originate from myeloid progenitor or osteal macrophages and is responsible for bone resorption (18, 19).
What cells do macrophages activate?
Macrophages interact with T cells in order to bring about T cell activation in target organs, and are themselves activated by inflammatory messenger molecules (cytokines) produced by the T cells. Macrophages produce toxic chemicals, such as nitric oxide, that can kill surrounding cells.
What is the role of cytokines in inflammation?
Cytokine is a general term used for small secreted proteins that are key modulators of inflammation. Cytokines are produced in response to invading pathogens to stimulate, recruit, and proliferate immune cells. Cytokines includes interleukins (IL), chemokines, interferons, and tumor necrosis factors (TNF).
What are the 5 cytokines?
Examine the five different types of cytokines found in the body: chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
Where is rankl found?
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.
What is the function of osteoclasts in bone tissue?
Osteoclasts are the cells that degrade bone to initiate normal bone remodeling and mediate bone loss in pathologic conditions by increasing their resorptive activity. They are derived from precursors in the myeloid/monocyte lineage that circulate in the blood after their formation in the bone marrow.
Do osteoblasts produce RANKL?
RANKL is a member of the tumor necrosis factor (TNF) super-family and is produced on osteoblasts and T cells.
What is RANKL in osteoporosis?
The interaction of RANK with its ligand (RANKL) has been identified as the final common pathway through which bone resorption is regulated [29]. By binding to its receptor RANK on osteoclastic precursors, RANKL controls the differentiation, proliferation, and survival of osteoclasts.
What activates RANKL?
RANK is also known to be expressed in skeletal muscle. The activation of RANKL/RANK signaling in skeletal muscle leads to the inhibition of myogenic differentiation through the activation of NF-κB, which results in skeletal muscle dysfunction and loss [97].
What are the 5 stages of bone healing?
- Hematoma formation.
- Fibrocartilaginous callus formation.
- Bony callus formation.
- Bone remodeling.
What is the process of bone remodeling and repair?
There are four stages in the repair of a broken bone: 1) the formation of hematoma at the break, 2) the formation of a fibrocartilaginous callus, 3) the formation of a bony callus, and 4) remodeling and addition of compact bone.
What are 4 factors that stimulate bone growth?
Summary. Bone contains several growth factors, including bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-β), insulin-like growth factors I and II (IGF-I and IGF-II), platelet derived growth factor (PDGF) and basic and acidic fibroblast growth factor (bFGF and aFGF).