Cellular structure of bone Flashcards
Hydroxyapatite
The principle mineral component of bone, composed of calcium and phosphate (Ca10(PO4)6(OH)2). Responsible for the hardness of bone.
Intramembranous ossification
The process by which flat bones develop as osteoblasts differentiate directly from mesenchyme precursors within mesenchymal connective tissue.
Endochondral ossification
The process by which long bones develop via the conversion of a cartilage model into bone
Chondrocyte
Mature cartilage cell. Produces cartilage matrix. Undergoes hypertrophic differentiation in the growth plate to allow linear growth
Growth plate
Specialised cartilage structure found at the metaphysis of long bones between the ossification centers. Allows linear growth.
Osteocyte
Terminally differentiated osteoblasts encased within mature bone. They are connected via a network of dendritic processes that allow them to have a mechanosensory role. Thought to be the master regulators of bone remodeling.
• Embedded in lacunae in mature bone • Connected via processes through canalicular channels • Form a mechanosensory network throughout bone
Osteoblast
Bone cells responsible for secreting osteoid which is then mineralized to become mature bone.
• Secretes osteoid; the organic component of new bone • Osteoid is mineralised over time to become mature bone • Some osteoblasts are embedded in the new bone and differentiate into osteocytes • Secretes osteoid; the organic component of new bone • Osteoid is mineralised over time to become mature bone • Some osteoblasts are embedded in the new bone and differentiate into osteocytes
Osteoclast
Large, multi-nucleate cells responsible for resorption of bone.
• Giant multinuclear cells formed from the fusion of macrophages • They seal off a portion of bone beneath them • They secrete acids and enzymes to ‘resorb’ the sealed off bone
Osteoid
The organic matrix of bone, consisting mainly of collagen and other protein. Secreted by osteoblasts, which line the surface of newly-formed bone.
Bone remodeling
The skeleton is continually renewed throughout life via the bone remodeling cycle, a process whereby old or damaged bone is removed through osteoclastic bone resorption, and an equal amount of new bone is formed by the osteoblasts
What is bone?
• INORGANIC - 65%
– calcium hydroxyapatite (Ca10(PO4)6(OH)2)
– is storehouse for 99% of Calcium in the body
– 85% of the Phosphorus, 65% Sodium,
Magnesium
• ORGANIC - 35%
– bone cells and protein matrix
Bone types and classifications
• Anatomical bones – Flat, long, short/cuboid, irregular, sesamoid • Macroscopic structure – trabecular/cancellous/spongy – cortical/compact • Microscopic structure – Woven bone (immature) – Lamellar bone (mature) • Anatomical bones – Flat, long, short/cuboid, irregular, sesamoid • Macroscopic structure – trabecular/cancellous/spongy – cortical/compact • Microscopic structure – Woven bone (immature) – Lamellar bone (mature)
Bone types and classifications cortical and trabecular
CORTICAL • long bones • 80% of skeleton • appendicular • 80-90% calcified • mainly structural, mechanical, and protective
TRABECULAR • vertebrae & pelvis • 20% of skeleton • axial • 15-25% calcified • mainly metabolic • large surface area
The Geography of a Bone
diagram
Bone Development
• Bones develop throughout growth and into adulthood
– Growth plate fusion and ossification completes development
– Clavicles growth plates fuse at ~20 years old
• Intramembranous ossification
– Direct differentiation of osteoblasts from connective tissue
– Flat bones
• Endochondral ossification
– Bones form from a cartilage model
– Long bones
Endochondral ossification
diagrams
what does the growth plate do?
Growth plate allows rapid linear growth
diagrams
The specialised bone cells
Osteocytes - mechanosensory network
embedded in mature bone
Osteoclasts - multinuclear cells that
resorb/remove bone
Osteoblasts - produce osteoid to form
new bone
why do we need a remodelling cycle?
• The skeleton is not a fixed or stagnant organ, it is dynamically
regulated to maintain health
• Small portions of bone are constantly being removed and
replaced
– Your whole skeleton has been replaced after 7 years
• This is done by the specialised bone cells via the bone
remodelling cycle
The Bone Remodelling Cycle
diagrams
Control of bone remodelling
Endocrine
• Estrogen, Thyroid hormone, PTH
Paracrine
• RANKL, Wnt signalling
Osteoclast differentiation and RANKL
• RANK receptor – Activation required for osteoclast differentiation and survival. • RANK Ligand – produced by osteocytes and osteoblasts • OPG (osteoprotegerin) – decoy receptor for RANKL also produced by osteocytes and osteoblasts.
Wnt signalling and bone formation
• Highly complex pathway involved in many different organ systems • Stimulates osteoblast differentiation • Inhibited by Sclerostin and Dkk-1
Osteocytes as key regulators of remodelling
diagram
Osteocytes as key regulators of remodelling
diagram
Bone disorders - Osteopetrosis
• LRP5 activating mutations
• van Buchem’s and SOST
• Defined as having a bone mass greater than 2.5 SD below average
peak bone mass
• Estimated that it will effect 1:2 women and 1:5 men.
– Causes 500,000 low impact bone fractures every year in the UK
• Can be primary (menopause, aging), or secondary (drugs, disease,
lifestyle)
diagrams