Bone Histology & Intramembranous Ossification

Question 1

Bones are \_\_\_\_\_ of the skeletal system
Individual bones are made up of:
1)\_\_\_\_\_ tissue
2)Bone \_\_\_\_
3)\_\_\_\_\_\_\_
4)\_\_\_\_\_\_\_\_

Answer 1

unit

1) Bone tissue
2) Bone marrow
3) Cartilage
4) Periosteum

Question 2

Physical Properties of bone:

1) ______: Resistance to compression, shear & tensile strength
2) Reservoir for _____ and ______
3) Adaptable to ______ and weight _____ via bone _____
4) Able to self-_______

Answer 2

1) Strength:
2) Calcium; Phosphate
3) Adaptable to growth and weight changes via remodeling
4) Able to self-repair

Question 3

Functions of bone:

1) ________ for the brain and internal ______
2) Attachment site for _______ allowing the _____ of limbs
3) Defense against _______
4) Endocrine ________
5) ________

Answer 3

1) Protection; organs
2) muscles; movement
3) acidosis
4) homeostasis
5) Hearing

Question 4

Bone Types
1) Immature Bone:
-_____/______: The first type of bone that will get deposited and gets remodeled by osteoblasts and osteoclasts into a mature bone
2) Mature Lamellar Bone:
_____/______: Forms the outer core of bone providing rigidity and strength
____/____/___: Adjacent to the bone marrow and is light-weight and involved in Calcium homeostasis

Answer 4

• Woven/Fibrous Bone
• Cortical/Compact Bone
• Trabecular/Cancellous/Spongy Bone

Question 5

Compact Bone

• Does not have ______ or ______ in the bone matrix that are visible to the eye
• ______ AND _______
• Thick and wall the _______ of long bones
• Forms around the _______ of long bones

Answer 5

• Spaces; hollows
• Lamellar and Haversian
• Diaphysis
• Epiphyses

Question 6

Spongy/Trabecular/Cancellous Bone

• Delicate network of ______ which branch and intersect to form a ______ like tissue that is _____ to the naked eye
• _____ of the Epiphyses contains mainly spongy bone in contact with the _____ ______
• _______ but NOT ________

Answer 6

• Trabeculae; sponge; visible
• Inside; Bone marrow
• Lamellar; Haversian

Question 7

Structure of a Flat Bone:

• External and internal surfaces of flat bones are composed of ________
• _____: Middle spongy layer
• ______ layer may fracture and the ______ bone may be crushed but the ____ bone layer and brain can be unharmed from head impacts

Answer 7

• Compact bone
• Diploe
• Outer compact bone; spongy; inner compact

Question 8

Bone Components
Cells:
-Osteoblast lineage
\_\_\_\_, \_\_\_\_, \_\_\_\_\_
-Monocyte-macrophage lineage
\_\_\_\_\_
ECM:
Organic (\_\_\_\_):
-Fibers: \_\_\_\_\_\_ Collagen
-Ground Substance: \_\_\_\_\_\_; \_\_\_\_\_
Mineral:
-\_\_\_\_\_\_\_\_

Answer 8

• Osteoprogenitor cells, Osteocytes, & Osteoblasts
• Osteoclasts
• Osteoid
• Type I
• Glycosaminoglycans; Proteoglycans
• Hydroxyapatite; Ca(PO4)6(OH)3

Question 9

Bone Tissue Composition
-Cells ___ % & matrix ____%
-Water ____% , Mineral ____%, & Organic_____%
-Organic composition:
Collagen____%, Proteoglycan ____%, & Protein______%

Answer 9

• 2% cells; 98% matrix
• 10% water; 70% mineral; 20% organic
• 90% Type I Collagen; 1% Proteoglycans; 9% Proteins

Question 10

Osteogenic Lineage

• Osteogenic Cells: Are found in the ______ & ______, arise from embryonic _________ cells, & multiply continuously and differentiate into ______ in response to _____ or ______; aka _____ cells
• Osteoblasts: Produce an ECM of ______ % fibers and ______% minerals, and are highly _______
• Osteocytes: _______ that are ______ in their secreted matrix and located in ______, the _____ differentiated state of _____, and are _______
• Spicule: ________, newly formed pieces of _____

Answer 10

• Endosteum; Periosteum; Mesenchymal; Osteoblasts; stress; fracture; Osteoprogenitor Cells
• ~35% Collagen; ~65% hydroxyapatite; secretory
• Osteoblasts; embedded in their matrix; lacuna; final; Osteoblasts; quiescent
• Isolated; bone

Question 11

Osteoblasts

• Derived directly from_____
• Epithelial-like _____ or _____ shaped cells in ______layers at sites of _______ bone formation
• Polarized cell with ECM released at the ____/_____ interface (_____ surface)
• Synthesizes ______, ______, & controls _______ of the matrix
• Osteoid is composed of: _____, ______, & ______
• Mineralized part of the bone is _______ dense and appears ______

Answer 11

• Osteoprogenitor Cells
• Cuboidal; columnar; monolayers; active
• Cell/bone; basal
• Osteoid; non-collagenous proteins; mineralization
• Type I Collagen; Glycosaminoglycans; Proteoglycans
• Electron; Black

Question 12

Osteocytes

• Derived from ______
• _________: Incapable of cell division, but are active ______ & ________
• Highly branched ______ with ________ extensions entering the ________ of the bone matrix
• Maintains the bone _____ & are responsible for bone _____

Answer 12

• Osteoblasts
• Terminally Differentiated; metabolically; biochemically
• Cell wall; cytoplasmic; canaliculi
• ECM; turnover

Question 13

Bone Mineral Matrix

• _____/_____ (65%): is composed of ______, a form of _______ ________
• Bone without _______ will be very flexible and bend since it’s only composed of ________ Collagen and will behave more like ________
• ________(35%): is composed of _______ Collagen and without it would be very ____ and cannot resist ______ or ______ since it’s lacking ______ and ________; _______ proteins, and _________

Answer 13

• Inorganic/Mineral; Hydroxyapatite; Calcium Phosphate
• Hydroxyapatite; Type I; cartilage
• Organic; Type I; brittle; stress; impacts; reinforcement; elasticity
• Non-collagenous
• Glycosaminoglycans

Question 14

Non-Collagenous Proteins in Bone ECM

• ______, _______, & _______
• Bone ________-
• _________ & _________

Answer 14

• Osteocalcin; Osteopontin; & Osteonectin
• Sialoprotein
• Growth Factor; Cytokines

Question 15

Glycosaminoglycans in Bone ECM

• ________ Sulfate
• ________ Sulfate
• _________ Acid

Answer 15

• Chondroitin Sulfate
• Keratan Sulfate
• Hyaluronic Acid

Question 16

Formation of Bone Mineral Matrix

• ________: Precipitation of ________ _______ & growth ________ Crystals
• Calcium Phosphate is extremely ______ and will spontaneously ______ at high [_____] or high [______]; & precipitates as _______ _____ ______ that is NOT usable by bone
• ________: Deposition of _____ ________ that can be deposited in normal or pathological conditions
• In non-mineralizing tissue, ______ ______ precipitation is prevented by crystal growth inhibitors like ________, which is very common in the ________
• In mineralizing tissue, ______ ________: Enzyme that destroys the crystal growth inhibitor _________, and is produced by ___________
• Marker for ______ activity is [______ ________]; these cells produce both _______ _____ & _______ to control the rate of _________ Crystal growth

Answer 16

• Mineralization; Calcium Phosphate; Hydroxyapatite
• Insoluble; precipitate; Calcium; Phosphate; Amorphous Calcium Phosphate
• Calcification; Calcium Carbonate
• Calcium Phosphate; Pyrophosphate; blood
• Alkaline Phosphatase; pyrophosphate; Osteoblasts
• Osteoblast; Alkaline Phosphatase; Alkaline Phosphatase & Pyrophosphates; Hydroxyapatite

Question 17

• Mineralization occurs in the ECM between _______ fibrils and requires _______: Specialized _____ & _____ that aid in the precipitation of _______ ________ from Amorphous _______ _______
• Locations of mineralization in the ECM: Within the _____ _____ separating Collagen molecules within Collagen fibrils; between _____ Collagen molecules; & the space between adjacent ______
• ______ Collagen Fibrils are thinner than _________ Collagen

Answer 17

• Collagen; nucleators; phospholipids; proteoglycans; Crystalline Hydroxyapatite; Calcium Phosphate
• Hole zones; adjacent; fibrils
• Non-mineralized; mineralized

Question 18

• The _____ of the mineralized matrix acts as the ______ for continuous growth and deposition
• ______ bands are layers of ECM that have not _______
• Uses ______ ______ and not electrons
• The layers contain _______ & ______ cells
• The layers are considered ______

Answer 18

• edge; nucleator
• White; mineralized
• Polarized light
• Osteoblasts; Osteocytes
• Lamellar

Question 19

Osteoclasts

• Derived from a _____ _____ stem cell; a ________/_______ colony forming unit (GM-CFU)
• The Monocyte Progenitor Cell may differentiate into either ______ or _______ depending on the signals received
• ___________:Travel directly through the bone marrow to the________ _______ surfaces, or via the vascular system to the ______ _____ and other bones where they may be needed like flat bones
• Mature Osteoclasts arise from the fusion of Preosteoclasts’ ______ ______ to form a multi-______ giant cell
• Responsible for bone ______ associated with bone ______, ______, and pathology
• Cross-talk between ______ and ______ regulates the process of final differentiation of ______

Answer 19

• Pluripotent Hematopoietic; Granulocyte/Macrophage
• Premonocytes; Preosteoclasts
• Preosteoclasts; Trabecular bone; Cortical Bone
• Plasma membranes’; nucleated
• Modeling; remodeling
• Osteoclasts; Osteoblasts; Osteoclasts

Question 20

Osteoclast Features:

• ________ ______: The cavity the Osteoclasts make on the bone facing the active side of the cell; aka the _______ _____ or ______ ______
• Active facing surface of the bone forms a ____ ____, this increases the ____ _____ in contact between the Osteoclast and bone matrix making resorption more efficient, and are created from _____ of the Osteoclasts
• _______ _______: Structure of the Osteoclasts that isolates the area of the bone being dissolved; composed of ____ ____ located at the surface of lacuna
• Osteoclasts are multi-____ rich in ______ and contain many _____ ______ containing the enzymes; prominent ______ ___

Answer 20

• Howship’s Lacuna; Subosteoclastic Compartment; Resorption Bay
• Ruffled border; surface area; extensions
• Sealing zone; actin filaments
• Nucleated; mitochondria; secretory vesicles; Rough ER

Question 21

• Dissolved components of the bone matrix: ______ & ______ ____, accumulate in the _____ ____ and are reabsorbed into the ____
• Reasons Osteoclasts need a lot of ______: CO2 to form _____ ______ & ____ ions; a lot of _____ is needed to produce _____

Answer 21

• Calcium; amino acids; interstitial space; blood

- Mitochondria; Carbonic Acid; Hydrogen; ATP; CO2

Question 22

2 Methods of Bone Resorption

• ____ & _____ destruction of the Osteoid via _____ & non-_____ enzymes
• Chemical solution of ____ to degrade _______

Answer 22

• Biochemical; enzymatic; lysosomal; non-lysosomal

- HCl; Hydroxyapatite

Question 23

Steps of Resorption

1. Osteoclasts create the ___ ___
2. _____ _____ is created to seal off the cavity (_____ ____) from the non active part of the Osteoclast; ____ in the Osteoclast and _____ (non-collagenous protein in the bone matrix) are bound to each other via αvβ3 _____
3. A _____-____ exchanger maintains cytoplasmic __ neutrality
4. A chloride channel facing ____ ____ prevents an excessive rise of ___ in the Osteoclasts
5. ______ ______: Releases protons into _____ ____ via an ATP-dependent Pump to create an _____ environment (pH __) to solubilize ______ bone, done by catalyzing the reaction of CO2 + H2O –> ___ + ___; both CO2 + H2O are products of the ____ Cycle and _____ ____ from mitochondria
6. ______ is exchanged for chloride in a 1:1 ratio, this makes Howship’s Lacuna very acidic since the H+ & Cl- join to form ____ which degrades the bone
7. ______ enzymes (____ & ____) are released to degrade Collagen, and non-_____ enzymes (________ & _____) degrade non-______ proteins

Answer 23

1) Ruffled border
2) Sealing zone; Howship’s lacuna; actin; Osteopontin; Integrin
3) Bicarbonate-Chloride; pH
4) Howships’ Lacuna; pH
5) Carbonic Anhydrase II; Howships’ Lacuna; acidic; 4.5; mineralized; H+; Bicarbonate (HCO3-); TCA; Oxidative Phosphorylation
6) Bicarbonate; HCl
7) Lysosomal; Proteinases; Phosphatases; non-lysosomal; Metalloproteinase 9; Cathepsin K; non-collagenous

Question 24

-Bone can be remodeled to: release ______, & sustain _____ _____ from being active

Answer 24

-Calcium; mechanical stress

Question 25

Steps of Osteoblast Regulation of Osteoclast Differentiation: 1) ________ derived from bone marrow express ________ on their surface which can bind the _____ ligand synthesized by ______ 2) Binding induces the ______ to become a ______ and induces the expression of ______ on the surface of the Macrophage. 3) _____ binds to _____ on the surface of the macrophage stimulating it to become an _____ precursors. _____ is on the surface of ____, _____, & _____. 4) ______ simultaneously secretes _______: A glycoprotein that binds to ____ on ______ with a much higher affinity than _____; this method helps _______ regulate the population of ________. 5) ______/______ Osteoclasts uncouple from the ______ 6) Maturation of Osteoclasts is complete when the _____ ____ & ____ ____ appear

Answer 25

1) Monocytes, Macrophage Colony-Stimulating Factor (M-CSF) Receptor; M-CSF ligand; Osteoblasts 2) Monocyte; Macrophage; RANK 3) RANKL; RANK; Osteoclast; RANKL; Osteoblasts; T-lymphocytes; Stromal Cells. 4) Osteoblasts; Osteoprotegerin (OPG); RANKL; Osteoblasts; RANK; Osteoblasts; Osteoclasts 5) Resting/Non-functional; Osteoblasts 6) Ruffled Border; Sealing Zone

Question 26

Osteoblast/Osteoclast Disequilibrium Disorders - _____: Decreased calcification or density of bone due to decreases _____ activity &/or increased _____ activity - _______: Progressive reduction in bone quantity making them weak and susceptible to fracture due to decreased _____ activity - _______: Excessive formation of dense trabecular bone, due to ______ deficiency or inactivity

Answer 26

- Osteopenia; Osteoblast; Osteoclast - Osteoporosis; Osteoblast - Osteopetrosis; Osteoclast

Question 27

-________: Functionally and embryologically similar to the Perichondrium. Covers the ____ surface of the bone except for the _______ surfaces and attachment locations of ______ & ______. 2 components: 1) ____/_____: Contains ____ _____: Collagen-rich and anchors the _____ to the bone matrix; & blood vessels with some entering ____ ____. 2) ___/____: Embryo and post-natally contains ______ that will differentiate into Osteoblasts; in adults contains inactive CT cells with Osteogenic potential and respond to bone injury and aid in repair -_______: CT that covers the spongy walls of the _____ ____ cavity, and extends into all bone cavities including the _____ ____

Answer 27

- Periosteum; Outer; articular; tendons & ligaments - Outer/Fibrogenic Layer; Sharpey's Fibers; periosteum; Volkmann's Canals - Inner/Osteogenic Layer; Osteoprogenitor Cells - Endosteum; bone marrow; Haversian Canals

Question 28

Compact Bone - Outside is where the ______ is located - ______: Circular growth rings surround Haversian Canals - Highly ______ unlike cartilage - Compact bone has _____, making compact bone _____ AND _____ - ____/_____: Basic structural unit of compact bone, cylinders of bone tissue form from concentric ____ of ____ & matrix arranged around a central/______ _____ - ________: Lined with endosteum and contains a neurovascular bundle - ________: Contains an artery, vein, nerves, and lymphatic vessels - _______ are connected to each other and their blood supply by pseudopods within _____ - _____/______: Perpendicular branches of the ______ _____ connecting 2 _____ ______ and thus 2 _____ to one another

Answer 28

- Periosteum - Lamella - Vascularized - Osteons; Lammela Haversian - Osteon/Haversian Systems; lamella; Osteocytes; Haversian Canal - Haversian Canal - Neurvascular bundle - Osteocytes; canaliculi - Perforating/Volkmann's Canals; Haversian Canals; Haversian Canals; Osteons

Question 29

Haversian Systems - Mineralization prevents _____ of minerals and nutrients - Difference from ______ is that diffusion can take place - ____ ____ within Haversian Canals provides _____ to Osteocytes, which get transported through a chain of ___ ______ away from Haversian Canals and towards Osteocytes. The transport system is limited to a distance of ______ - _____ ____ of Osteocytes are embedded within ______ connecting cell bodies - _______: Cavities in the bone matrix surrounded by mineralized bone, that perforates the bone connecting ______ to one another and are filled with ___ _____ during life; nutrients _____ from capillaries to to ends of cell processes - ____ _____ are at the contact points of ______ processes, connecting them together

Answer 29

- Diffusion - Cartilage - Blood vessels; nutrients; cell processes; 100 micro meters - Cell processes; canaliculi - Canaliculi; cell bodies; cell processes; diffuse - Gap junctions; Osteocyte

Question 30

Spongy Bone - Are ____ but NOT _____ - ______: Sponge-like appearance formed by rods and plates of bones, and develop along bones' _____ of _____ where strong forces act - Spaces among the trabeculae are filled with ____ ____ - ____-weight but strong

Answer 30

- Lamellar; Haversian - Trabeculae; lines of stress - Bone Marrow - Light-weight

Question 31

Osteogenesis: Bone Formation - Intramembranous Ossification: Forms ____ & ____ bones, like the _____ & _____. Forms well-vascularized primitive CT _____. Bone formation does NOT require a ______ template, and uses the direct differentiation of cells within _______ into ______ - Endochondral Ossification: Forms ____ bones, like ____ bones and the ______ _____. Requires the replacement of a _______ ______ template with bone - Both intramembranous and endochondral ossification occur side by side, seen with ______ healing and the development of the _______

Answer 31

- Flat; short; skull; clavicle; Mesenchyme; Hyaline Cartilage; Mesenchyme; Osteoblasts - Long; axial; appendicular skeleton; Hyaline Cartilage - Fracture; mandible

Question 32

Steps of Intramembranous Ossification 1) Condensation of the ______ into soft sheets permeated with blood capillaries 2) Deposition of _____ by Osteoblasts on the _____ surface, the entrapment of the first _____ and formation of the ______ 3) Honeycomb of bony trabeculae is formed by continued ______ deposition; this creates _____ bone 4) Surface bone filled in by bone deposition converting ______ bone to ______ bone

Answer 32

- Mesenchyme - Osteoid; mesenchymal; Osteocytes; Periosteum - Mineral; Spongy - Spongy; compact

Question 33

Intramembranous Ossification of the Skull - ______ ossification is incomplete at birth, this facilitates passage through the _____ ____ - _______: Regions of ______ _____ that are soft regions of the skull. Usually have __ at birth, where most close by ___ months and all are closed by ___ months. _____ close when ___ ___ fuse together

Answer 33

- Cranial; birth canal | - Fontanel; dense irregular CT; 6; 12 months; 24 months; Fontanel; flat bones