6 Osteogenesis

• 1. Endochondral
• 2. Membrane (Dermal)
• most of the bones in the body are Endochonral: long bones of the extremities, ribs, other bones of the thorax, vertebrae, & pelvis
• most of the flat bones of the skull are Membrane bones & form completely differently than the endochondral bones

• Endochondral Ossification
• start with a cartilage template that resembles a small version of the adult bone & use it to deposit bone on
• bone initially deposited is called Woven bone
• after remodeling it BECOMES lamellar (compact or spongy)

• start with a cartilage template that somewhat resembles the adult bone that’s going to be formed
• 1. chondrocytes in the center of the cartilage (mini-bone template) begin to ENLARGE (hypertrophy); they will eventually die, & the cartilage in between them will become calcified
• that will make the region porous so blood vessels can enter, bringing with them osteogenic cells (blasts + clasts)
• 2. osteoblasts will start laying new bone on top of the calcified cartilage
• this forms the Primary Center of Ossification
• 3. at about the same time all that’s going on, the Periosteal Collar is being made; this is bone that’s forming around the shaft/diaphysis
• the collar is DE NOVO bone synthesis - new bone is made on the edge of hyaline cartilage (no template)
• perichondrium → periosteal collar → bony collar
• 4. the same events that occurred to form the Primary Center of Ossification now happen at the 2 Epiphyseal ends: hyaline cartilage chondrocytes hypertrophy, intervening cartilage calcifies, chondrocytes die, ingrowth of blood vessels + osteoprogenitor cells, new bone is laid down on top of calcified cartilage
• these are called the Secondary Centers of Ossification
• 5. a portion of hyaline cartilage called the Epiphyseal Plate is maintained between both Secondary Centers of Ossification & the central Primary Center of Ossification
• the Epiphyseal Plate is what allows long bones to grow in length
• 

• can see hyaline cartilage on the two ends
• however central hyaline cartilage contains much larger cells (hypertrophied)
• cartilage in between cells is going to become calcified (stains blue/purple instead of pink)
• chrondrocytes will die
• area becomes porous, allowing BVs to migrate in & bring with them osteogenic cells to build bone on the calcified cartilage

• 
• Resting: standard hyaline cartilage (see double Ds, there’s some division)
• Proliferating: when cells proliferate in earnest they do so along the long axis, parallel to the bone - resembles a “stack of coins” as opposed to just a clump of cells
• Hypertrophic: chondrocytes are much LARGER & the in between cartilage is darker than in the resting & proliferating zones - this is because it’s undergoing CALCIFICATION
• Calcified: calcified cartilage is the template upon which osteoblasts will lay down new bone; chondrocytes are dead in this type of bone
• the calcified end is closest to the Primary Center of Ossification (diaphysis)
• 

• osteoblasts laying down new bone on top of calcified cartilage - MIXED SPICULES
• 
• blue: CC (calcified cartilage) - blue because it has lots of sulfated proteoglycans, binds the eiosin
• pink: bone, more rich in cartilage so it binds the hemotoxalin
• you know this is new bone because of the osteoid being synthesized by osteoblasts

• stays the same thickness, just shifts ‘up’ toward the epiphysis
• there’s erosion of hyaline cartilage at the diaphyseal end, & addition of hyaline cartilage at the epiphyseal end

• there’s no longer proliferation of chondrocytes at the ‘epiphyseal’ (upper) end, but there’s STILL erosion of them at the diaphyseal end
• eventually the plate gets thinner & thinner → eventually disappears
• in adult bone there’s no evidence of it whatsoever

• bones remodel throughout life as well as to repair fractures & especially during development
• the woven bone initially deposited is very disorganized - doesn’t have the strength of lamellar bone
• both spongy & compact bone need to be remodeled after initial placement

• the bone collar is initially formed as SPONGY bone - have lots of marrow spaces
• these will eventually be filled in by osteoblasts until what’s left is compact (Haversian) bone
• but Haversian systems don’t come about UNTIL remodeling

• osteoclasts excavate a channel
• once there’s exposed bone, osteoblasts are recruited to the wall of the channel, line up & begin synthesizing bone
• some will get entrapped → osteocyte, while the rest continue to form the Osteon

• image shows Osteons (Haversian systems) in development
• faint blue/purple line shows the extent to which osteoclasts excavated the bone (initial channel that was created)
• osteoblasts lined up on that surface & laid down new bone
• some osteoblasts became trapped → osteocyte
• the rest can be seen synthesizing new bone (Osteoid)
• 

• during development, the spicules are small & not robust
• they need to enlarge & become thicker to form adult bone
• 
• there will be removal of woven bone by osteoclasts, & new lamellar bone will get deposited by osteoblasts
• space for red bone marrow still exists even in adult spongy bone

• builds the flat bones in the cranium & face
• bone formation will begin DE NOVO, from condensation of mesenchyme
• there’s NO cartilage template
• bone will be initially deposited woven, then remodeled into compact & spongy bone as needed
• have important difference in terms of bone building, but once Intramembranous bone is BUILT, it’s remodeled in the exact same way as Endochondral bone
• 

• see condensation of mesenchyme & cells differentiating into osteoblasts
• bone is initially made as woven spongy bone
• if the bone is supposed to become compact, the white spaces will be filled in, followed by remodeling to Haversian systems
• if the bone is supposed to stay spongey, then the marrow spaces would persist

periosteal (outer) lamellae lie beneath the periosteum while endosteal (inner) lamellae lie beneath the endosteum

• a thin layer of connective tissue that lines the medullary cavity
• endosteum have osteogenic capability (stem cells are available on all surfaces of bone tissue)

• a tough dense connective tissue that surrounds the outer surface of bone organs EXCEPT at articular surfaces
• it's anchored to the underlying bone tissue by bundles of collagen fibers (Sharpey fibers) which penetrate perpendicularly into the bone

• when primitive mesenchymal cells differentiate immediately into bone
• early on, mesenchymal cells differentiate into osteoblasts and lay down bone matrix
• as it is initially laid down, the bone is spongy & woven
• mesenchyme --> bone
• how flat bones of skull/jaw form

• when primitive mesenchymal cells differentiate first into chrondrocytes of hyaline cartilage
• they enlarge then die and leave behind cartilage matrix that becomes calcified (calcified MATRIX)
• this calcified matrix induces other mesenchymal cells to differentiate into osteoblasts
• these secrete bone matrix over the surface of calcified cartilage spicules
• mesenchyme --> hyaline cartilage --> bone
• how the long bones form

endochondral bone spicules have a calcified basophilic cartilage matrix core (it's the hallmark of newly made endocondral bone)

• 1) all compact bone tissue forms first as spongy bone
• 2) all bone tissue forms first as osteoid
• 3) all bone tissue grows by apposition only
• They're all TRUE