Bone Formation 101

So I noticed a bunch of you guys had some questions about bone formation – hope this answers most of your questions!

NOTE: this is endochondral ossification we’re talking about formation of bone from cartilage (hence “chondral” ending) o This process is for the formation of long bones

Flat bones are formed by intramembranous ossification. PRIMARY OSSIFICATION CENTRE 1. Starting with piece of hyaline cartilage in shape of future bone, in the region of the

diaphysis (middle narrow part), perichondrium is transformed into periosteum (black border)

a. Note: the whole piece of hyaline cartilage is surrounded by a perichondrium except at the two ends that will become the articular surfaces

2. Periosteum deposits bone inside the cartilage forming bone collar 3. Bone collar prevents diffusion of nutrients, cartilage dies (hypertrophy & cell death),

EMC becomes calcified 4. Blood vessels from perichondrium/periosteum invades empty space left by

degenerating chondrocytes, carrying with them anything on bone surface inside.

Stuff dragged in include: osteoprogenitor cells, osteoblasts 5. Osteoprogenitor cells differentiate into osteoblasts divide & secretes ECM

Completes formation of primary ossification centre SECONDARY OSSIFICATION CENTRE 1. Takes place at level of epiphysis of future bone 2. Cartilage degenerates since it also gets choked off from nutrients by the bone collar

(happens later than primary ossification centre – hence “secondary”) 3. Blood vessels again from the outside (perichondrium) also invade the space as the

cartilage deteriorates 4. The only cartilage left is at the articular surface and epiphyseal plate (all other

cartilage degenerates – remember it start off as a piece of hyaline cartilage!)

Epiphyseal plate: layer of cartilage in between primary + secondary ossification centre (cartilage persists until 20 years of age)

Cartilage at the surface is classified as “articular” cartilage even though it began as hyaline cartilage!

Epiphyseal plate is still “hyaline” cartilage since the perichondrium is intact

Metaphysis: area between epiphysis & diaphysis

Primary ossification centre

(bone formation inside area

enclosed by bone collar or

region known as shaft

(diaphysis) of the bone.

Secondary ossification centre –

bone formation at the two ends

of the bone (epiphysis)

Epiphyseal plate is “fused” – see how there’s no more cartilage! This bone can’t get any longer.

After that… (we’re at the stage of second last diagram above) 1. After the primary and secondary ossification centers have done their job – you end up a piece of bone formed from the chunk of hyaline cartilage

you started off with. 2. The long bone then lengthens via the action of the epiphyseal plate 3. As the chrondrogenic layer forms more hyaline cartilage, the epiphseal plate “grows” outwards (see [1] below) 4. However, the overall width of the plate does NOT increase because the other end is being chew up by osteoclasts (see [2]) – (so this is after the

chondrocytes go through the layers of hypertrophy, cell death, etc.) Putting it in Perspective – what it really looks like

plate!)

Cartilage at the head of the bone remains – this is the articular cartilage (no perichondrium!)

Head of bone (epiphysis) becomes filled with spongy bone.

[1] Direction of growth (due to cartilage proliferation)

[2] Big fat osteoCLASTS chewing everything up at this end

Skeletal muscle!

Zoom in on the black box – epiphyseal plate

Shaft (diaphysis) becomes compact bone

Mixed spicules (mixture of cartilage & bone) – osteoclasts chewing away in this region.

The Epiphyseal Plate

Zones in Epiphyseal Plate 1. Zone of resting cartilage

Light pink, with chondrocytes trapped in lacuna, normal cartilage 2. Zone of proliferation

Chondrocytes trapped in lacuna are proliferating looks like stack of coins, very adidophillic

Pushes resting layer up 3. Zone of hypertrophy

Lacunas start to fill up with fluid more space seen around chondrocytes, paler 4. Zone of cell death

Chondrocytes start dying after death occurs in primary centre

Nuclei disappears, cell ruptures

Cells die due to hypertrophy above it NOT because of bone collar (which doesn’t cover epiphysis) 5. Zone of mixed spicules (indistinct)

Osteoblasts: got in via blood vesselsaround periphery of cartilage, lays down bone matrix (darker) over calcified cartilage matrix (lighter)

Osteoclasts: at the same time chew up newly synthesize bone + calcified cartilage o Large, acidophilic, many nuclei

Calcified cartilage: appears purple

Zone of mixed spicules: mixed bone + calcified cartilage o Pieces of bone formed when ECM engulfs osteocyte, consists of woven bone (immature), NOT

lamellar bone (compact bone of diaphysis)

NOTE: while bone is forming from cartilage and lengthening – the shape undergoes remodeling at the

same time there’s a slide in your lectures that explain this pretty well. =)

Hope this clarifies things! You guys better get 100% on the short answer if bone formation appears. =)

Email me if you find anything ambiguous or discrepancies – this stuff is based on last year’s lectures so I don’t know if he introduced anything new.

heidi.wat@mail.mcgill.ca