What are the primary functions of bone tissue?
- Support
- Movement
- Protection
- Mineral storage
- Energy storage
- Blood cell formation
- Energy metabolism
What are the two primary components of the ECM (matrix component of bone)?
- Organic components (35% of tissue mass)
- Inorganic components (65% of tissue mass)
Organic Components of Bone ECM
- Consists of organic substances, primarily collagen, which contributes to the flexibility and tensile strength that allow bone to resist stretching and twisting
- Also contains: Osteonectin and Osteocalcin, Proteoglycans, Sialoproteins, Osteopontin, and thrombospondin
What is the role of the organic components of the Bone ECM: Osteonectin and Osteocalcin?
Aid in hydroxylapatite crystallization and binds calcium
What is the role of the organic component of the Bone ECM: Proteoglycans?
Bind growth factors (TGF-β)
What is the role of the organic component of the Bone ECM: Sialoproteins, Osteopontin, and Thrombospondin?
Mediate osteoclast adhesion to bone surface (bind osteoclast integrins)
Inorganic Components of Bone ECM
- Consists of inorganic hydroxyapatites or mineral salts, primarily calcium phosphate (some calcium carbonate, K and Mg)
- present as tiny crystals to lie in and around collagen fibrils in the ECM
- Pack tightly, contributing to the hardness of bone and its ability to resist compression
Osteogenic Cells
- Stem cells that differentiate into bone-forming osteoblasts
- Located within the inner layer of the periosteum
- Precursor to osteoblasts and osteocytes
- Only bone cells that undergo cell division
What are Osteoblasts derived from?
Mesenchymal stem cells
Osteoblasts
- Cuboidal shaped
- Directly regulate bone matrix synthesis and mineralization (synthesize components of ECM)
- Indirectly control bone resorption through release of paracrine factors that regulate osteoclasts (RANKL/OPG)
What 3 things can Osteoblasts become?
- Osteocytes: embedded in matrix
- Bone lining cells: protect inactive bone surfaces
- Initiate apoptosis
Osteocytes
- Terminally differentiated osteoblasts that have become trapped within newly deposited bone matrix
- Smaller than osteoblasts and contain projections into the matrix (allows them to interact with the ECM and respond to changes)
- Respond to mechanical loading by releasing paracrine factors that stimulate and coordinate bone remodeling and calcium release
What are Osteoclasts derieved from?
Mononuclear cells in bone marrow
Osteoclasts
- Cells that resorb mineralized bone matrix by secreting acid and lytic enzymes
- Multinucleated
What controls differentiation of cells into osteoclasts?
Receptor Activator of Nuclear Factor κβ (RANKL) which is released from Osteoblasts
What inhibits differentiation of cells into osteoclasts?
OPG – sequesters RANKL
Osteogenic Cell
(1) Function:
(2) Location:
(1) Develop into osteoblasts
(2) Deep layers of the periosteum and the marrow
Osteoblast
(1) Function:
(2) Location:
(1) Bone formation
(2) Growing portions of bone including the periosteum and endosteum
Osteocytes
(1) Function:
(2) Location:
(1) Maintain mineral concentration of matrix
(2) Entrapped in matrix
Osteoclasts
(1) Function:
(2) Location:
(1) Bone resorption
(2) Bone surfaces and site of old or injured bone matrix
Wolff’s Law
- “bones that bear a lot of weight remodel at a high rate”
- bone reacts to mechanical functional stress through an adaptive process resulting in a change of its external and internal architecture to better withstand stress
- if loading on a particular bone increases, the bone will remodel itself over a period of time to withstand greatest strength (to reduce fx) with least amount of material
Bone Remodeling
- the internal turnover of mineralized bone matrix – often leads to changes in the architecture of the bone
- occurs due to changes in stress and changes in hormones
- it is an ongoing process
- functions in: repairing microdamage, maintaining strength, maintaining serum calcium in normal physiological range, helps bones heal after a fracture
- high loading activities produce higher levels of bone remodeling which will increase bone deposition (ex. weight lifting)
Basic Remodeling Process (6 Steps)
(1) Microdamage or change in mechanical stress on bone matrix
(2) Osteoclast progenitors are activated
(3) Osteoclastic bone resorption occurs
(4) Reversal
(5) Osteoblastic bone formation
(6) Mineralization, osteocytogenesis
Steps:
(1) Osteoblasts sense microcracks
(2) Osteoblasts produce RANKL
(3) RANKL binds to RANKL receptors on nearby monocyte precursor cells, and induces these cells to form osteoclasts
(4) Osteoclasts secrete collagenase which digests collagen protein in organic matrix; leads to formation of “pits” on bone surface called Howship’s Lacunae, and release of Ca2+
(5) Osteoblasts also secrete Osteoprotegerin which binds to RANKL and prevents it from activating RANKL receptors, and they secrete Osteoid Seam which fills in the holes on the surface of the bone (osteoblasts sometimes get stuck in these holes and then they mature to osteocytes and stay in bone)
List the regulators (local or systemic) of bone modeling and remodeling
- Transforming Growth Factor- β
- Bone Morphogenic Proteins (BMPs)
- Osteoprotegerin (OPG)
- Fibroblast Growth Factors (FGFs)
- Insulin-Like Growth Factors (IGFs)
- Platelet-Derived Growth Factor (PDGF)
- RANKL
- Interleukins
- Parathyroid Hormone (PTH)
