Skeletal System and Skeletal Disorders 1 Flashcards
What are the functions of the skeleton?
Muscle attachment, locomotion and body shape.
Protection.
Mineral Storage.
Adaptive biological system.
Detects and processes multiple inputs to produce an appropriate response.
endocrine role
What are the two types of bone tissue?
Compact / cortical
Main weight bearing structure. (outside)
Trabecular / spongy / cancellous.
Main site of calcium exchange. Optimised to provide the greatest amount of support for minimum mass. Greater surface area and is the major sight of minerals. They form along the major strain patterns in accordance with mechanical inputs.
Organisation of bone tissue
Compact Bone:
Osteons: Compact bone consists of densely packed structural units called osteons or Haversian systems. Each osteon is a cylindrical structure oriented parallel to the long axis of the bone.
Central Canal: Within each osteon, there is a central canal (osteonic or Haversian canal) that houses blood vessels and nerves, providing nutrients and innervation to the bone tissue.
Osteocytes: Compact bone contains osteocytes, which are bone cells embedded within the mineralized matrix. Osteocytes communicate with each other through small channels called canaliculi.
Lamellae: The matrix of compact bone is organized into concentric rings called lamellae. These lamellae surround the central canal and provide strength and support to the bone.
Outer Layer: Compact bone forms the outer layer of most bones and provides structural support and protection.
Spongy Bone:
Trabeculae: Spongy bone, also known as trabecular or cancellous bone, consists of a network of bony struts called trabeculae. These trabeculae create a porous, lattice-like structure.
The spaces between trabeculae are filled with bone marrow, which plays a role in blood cell formation and storage of fat.
Osteocytes: Like compact bone, spongy bone contains osteocytes, but they are housed within the trabeculae rather than organized in osteons.
Less Organized Lamellae: The lamellae in spongy bone are less organized than in compact bone. Instead of concentric rings, trabeculae have a more irregular arrangement.
Inner Layer: Spongy bone is typically found at the interior of bones, especially in the epiphyses (ends) of long bones. It provides structural support while being lighter than compact bone.
Shock Absorption: Spongy bone is well-suited for bearing stress from multiple directions and providing shock absorption.
Red Marrow: The spaces within spongy bone contain red marrow, which is involved in the production of blood cells.
Describe the Four types of cells that compose bony tissue:
Where is bone marrow found?
osteocytes, osteoclasts, osteoprogenitor cells, and osteoblasts.
Bone marrow is found in both trabecular (spongy) and cortical (compact) bone. Trabecular bone, with its lattice-like structure, contains red bone marrow responsible for blood cell formation. Compact bone, forming the outer layer, has marrow concentrated in the medullary cavity, containing yellow marrow for energy storage.
Bone Cells;
bone marrow
osteoblastic lineage
osteoclastic lineage
Bone Marrow
Cell Types:
Erythrocytes: Red blood cells responsible for oxygen transport.
Lymphocytes: White blood cells involved in the immune system.
Cells of the Myeloid Lineage: A group of cells derived from the bone marrow that includes various blood cells, such as granulocytes, monocytes, and platelets.
Osteoblastic Lineage (Stromal):
Osteoblasts: Cells responsible for bone formation and mineralization.
Bone Lining Cells: Cells that may detect changes in the mechanical loading environment. They can expose the bone surface for resorption, which is a process related to bone remodeling.
Osteocytes: Considered the main mechano-sensitive cells in bone. Osteocytes are embedded in the bone matrix and are involved in sensing mechanical forces or strains on the bone.
Osteoclastic Lineage (Myeloid):
Osteoclasts: Cells responsible for bone resorption. Osteoclasts break down and absorb bone tissue, contributing to the remodeling and maintenance of bone .
Physiological factors that impact on skeletal homeostasis
Fluctuations in serum calcium levels.
Changes in mechanical loading environment. (heavy lifting can increase you skeleton size)
Repair of micro fractures. Repetitive force, often from overuse — such as repeatedly jumping up and down or running long distances.
Hormonal status. Overactive parathyroid glands or hyperparathyroidism can cause excessive bone breakdown and increase the risk of fractures.
Osteoblastic lineage
*Derived from stromal precursors that are capable of forming either osteoblasts or adipose cells.
*Osteoblasts synthesise the organic matrix of bone (osteoid) and control its mineralization.
*When osteoblasts finish making new bone they can differentiate into;
Osteocytes
Bone lining cells
or undergo apoptosis
Osteoblasts:
Function: Build and mineralize bone tissue (pumps calcium and phosphorous into it)Calcium hydroxyapatite providing mechanical competency.
Bone Lining Cells:
Function: Detect changes in mechanical loading and contribute to bone remodeling.
Osteocytes:
Function: Mechano-sensitive cells embedded in bone matrix, regulating bone structure in response to mechanical forces.
Regulators of osteoblast differentiation
Systemic regulators
Parathyroid hormone, leptin, thyroid hormone, growth hormone, androgens and oestrogen. Promote osteoblast differentiation, might not work directly to promote this, they might work with local regulators which act as mediators.
Local regulators
Insulin like growth factor I, PTHrP, hedgehog proteins, sclerostin, BMPs, interleukin-6 and TGF-b.
Signal transduction and transcription factors
CBFA1 (RUNX2), osterix, wnt and frizzled.
Systemic regulators influence local regulators.
Local regulators transmit signals to cells.
Signal transduction factors regulate gene expression for bone development.
Describe Bone formation
*Sequential process
*Osteoid formation
Inorganic
*Mineralization
Calcium hydroxy-apatite
Osteoblast differentiation
Initiation:
Mesenchymal stem cells commit to the osteoblast lineage.
Transcription factors Cbfa1 (RUNX2) and Osterix (OSX) are activated.
Proliferation and Differentiation:
MSCs proliferate and progress to pre-osteoblasts.
Cbfa1 and Osterix drive differentiation.
Matrix Synthesis:
Pre-osteoblasts synthesize extracellular matrix, including collagen and osteoid.
Mineralization:
Hydroxyapatite crystals are deposited in the matrix.
Osteocalcin is produced and incorporated.
Maturation into Osteoblasts:
Pre-osteoblasts mature into functional osteoblasts.
Continue synthesizing bone matrix proteins.
Bone Formation:
Osteoblasts actively contribute to matrix mineralization.
Participate in bone remodeling.
Transition to Osteocytes:
Some osteoblasts become osteocytes embedded in the matrix.
Function as mechanosensors in bone.
Key Molecular Players:
Cbfa1 (RUNX2): Essential for lineage commitment.
Osterix (OSX): Drives osteoblast differentiation.
BMPs: Induce osteoblast differentiation.
Wnt/β-catenin Signaling: Regulates osteoblast differentiation and bone formation.
Cells involved in bone resorption
Form from pluripotent CD34+ mononuclear phagocyte precursors which can form many myeloid cell types.
Precursor differentiation is controlled by the cytokines/growth factors that it encounters at a specific stage of its development.
There are two different pathways
1. myeloid diverse range of mature cells= red blood cell, monocytes, neutrophils etc…
lymphoid=b-cells, t-cells etc…
osteoclasts
Responsible for bone resorption.
Can be multinuclear. Are TRAP positive, express calcitonin receptors, cathepsin K (break down organic component of bone matrix) and other proteinases, it also releases hydrochloric acid. (pinky red cells when they are stained).
Process of bone resorption
- Osteoclast attaches to surface through a5b3 integrin interaction with RGD containing proteins. Bind tightly to prevent HCL escaping causing an inflammatory response
- Polarisation of osteoclast formation of ruffled border, actin ring and sealed zone.
- Acidification of the sealed zone by active transport of H+ to breakdown mineral component of bone. Oc pH maintained by Cl-/HCO3– exchanger on basolateral surface.
4. Release of cathepsin K and other proteases that digest collagen.
- Creates a resorption pit 4-5 mM deep.
Regulation of osteoclasts
Physiological regulators of osteoclast differentiation and bone resorption
*Low serum Ca2+ levels. (Calcium homeostasis)
*Decreases in mechanical loading
Pathological regulators
*Disruption of steroid hormone levels
*Inflammation (osteomyelitis)
*Cancer (secondary, such as breast and prostate-they are targeted to bone, breast cancer stimulates bone resorption so there are bone complications after breast of bone cancer)
Osteoclasts and Ca2+ homeostasis
Calcitonin also regulates osteoclast activity. Increased [Ca2+] stimulates calcitonin formation which directly inhibits osteoclast activity.
Fall in [Ca 2+] leads to PTH release from parathyroid glands.
This elevates [Ca 2+] through a variety of mechanisms
*Promotes bone resorption.
*Activates 1,25 Vit D3 in kidney which increase intestinal uptake of Ca 2+.
*Increases renal reabsorption of Ca 2+
Regulation of osteoclast formation. What was found?
Known that osteoclast don’t express PTHR.
McSheey and Chambers in 1988 showed that PTH acts indirectly through osteoblast to stimulate osteoclast formation.
Osteoblastic factor was sort for 10 years.
