Physiology of Bone Flashcards
1
Q
What are the main functions of bone?
A
- support
- movement
- protection
- mineral storage
- blood cell formation
- energy storage
- energy metabolism
2
Q
What are the 4 different types of bone cells and their general function?
A
- osteoclast: resorbs bone
- osteogenic cell: stem cell
- osteoblast: forms bone matrix
- osteocyte: maintains bone tissue
3
Q
What are the organic components of bone ECM?
A
(~35% of tissue mass)
- organic substances, particularly collagen, contribute to the flexibility and tensile strength that allow bone to resist stretching and twisting
- osteonectin and osteocalcin: aid in hydroxyl apatite crystallization and bind calcium
- proteoglycans: bind growth factors (TGF-beta)
- sialoproteins, osteopontin, and thrombospondin: mediate osteoclast adhesion to bone surface (bind osteoclast integrins)
4
Q
What are the inorganic components of bone ECM?
A
(~65% of tissue mass)
- consists of inorganic hydroxyapatites or mineral salts, primarly calcium phosphate (some calcium carbonate, K, and Mg)
- present as tiny crystals to lie in and around collagen fibrils in ECM
- pack tightly, contributing to hardness and ability to resist compression
5
Q
- type of bone cell
- stem cells: differentiate into bone-forming osteoblasts
- location: within inner layer of periosteum and the marrow
A
osteogenic cell
6
Q
- type of bone cell
- cuboidal shaped cells that are dervied from mesenchymal stem cells
- location: growing portions of bone including, periosteum and endosteum
- directly: regulate bone matrix synthesis and mineralization
- indirectly: control bone resorption through release of paracrine factors that regulate osteoclasts (RANKL/OPG)
- will become: osteocytes (embedded in matrix), bone lining cells (protect inactive bone surfaces), and initiate apoptosis
A
osteoblasts
7
Q
- type of bone cell
- terminally differentiated osteoblasts
- location: trapped within newly deposited bone matrix
- smaller than osteoblasts and contain projections into matrix
- respond to mechanical loading by releasing paracrine factors (stimulate and coordinate bone remodeling and calcium release)
- maintain mineral concentration of matrix
A
osteocytes
8
Q
- type of bone cell
- specialized cells that resorb mineralized bone matrix
- location: bone surfaces and site of old injured bone matrix
- secrete acid and lytic enzymes
- multinucleated, derived from mononuclear cells in bone marrow
- differentiation controlled by receptor activator of nuclear factor κβ (RANKL) from osteoblasts (can be inhibited by OPG which sequesters RANKL)
A
osteoclasts
9
Q
- law that states: 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 with least amount of material
A
Wolff’s Law
10
Q
What is the importance of the bone remodeling cycle?
A
the cycle is important to repair microdamage, maintain strength, and maintain serum calcium in normal physiological range
11
Q
Describe the bone remodeling process:
A
- microdamage or change in mechanical stress occurs
- activation of osteoclast progenitors
- osteoclastic bone resorption
- reversal (apoptotic osteoclast along with growth factors activates mesenchymal stem cell to differentiate into osteoblasts)
- osteoblastic bone formation occurs
- mineralization and osteocytogenesis occurs
12
Q
Describe the RANKL/OPG regulation on bone remodeling:
A
- RANKL is produced by osteoblasts: high driver of proliferation and differentiation of osteoclasts from progenitors (activated by RANKL, have a RANK receptor that binds to RANKL)
- OPG is a mock receptor for RANKL and sequesters it, preventing it from activating additional osteoclasts, thus preventing further bone resorption
- there is a ratio of RANKL to OPG to prevent overabundance of bone resorption
13
Q
- stimulate the proliferation and differentiation of osteoblasts and bone formation
- increase OPG production
A
transforming growth factors-β (TGF-β)
14
Q
- potent inducers of osteoblasts and bone formation
- regulate matrix production
- used clinically: rhBMP-2 in fracture healing and spinal fusion
A
bone morphogenic proteins (BMPs)
15
Q
- secreted from osteoblasts
- binds RANKL sequestering it and preventing osteoclast activation
A
osteoprotegerin (OPG)
22
Q
- specialized type of wound healing
- sequence of inflammation, repair, and remodeling
- healing sequence depends on amount of movement between fragments: limited movement (indirect healing) and no movement (direct healing)
A
fracture healing
23
Q
Describe the process of indirect (secondary) fracture healing:
A
5 stages
- tissue destruction and hematoma: tissue damage leads to increased blood flow and cytokines, causing a hematoma
- inflammatory phase (~1 week): driven by cytokines TGF-beta and PDGF, stimulates new blood vessel formation and recruit mesenchymal stem cells which proliferate and become osteoprogenitor cells, osteoclasts also recruited to clear out dead bone tissue
- soft callus formation (weeks 2-3): made up of fibrous connective tissue, limits movement of bone fragments
- hard callus formation (weeks 4-12): occurs when soft callus is replaced by bone matrix in the form of woven bone; produced by osteoclasts and osteoblasts by removing connective tissue and replacing it w/ bone matrix (RANKL and OPG play important roles in this phase)
- remodeling of bone (years): hard callus is replaced by additional bone remodeling (malar bone and angiogenesis)
