Type of bones

Flat bones have a dense (compact) periphery called the outer table and a cancellous interior, the diploë

The diploe is filledewith red bone marrow; where blood cells arise

Growth occurs by appositional growth on all surfaces

Long bones have a diaphysis (shaft) which becomes hollow (marrow)

After ossification begins, growth in length is primarily at epiphyseal plates

Appositional growth occurs on all outer surfaces of the periosteum or perichondrium making the bones thicker (and longer)

Bone is formed through a lengthy process involving ossification of a cartilage formed from mesenchyme. Two main forms of ossification occur in different bones, intramembranous (eg skull) and endochondrial (eg limb long bones) ossification. Ossification continues postnatally, through puberty until mid 20s. Early ossification occurs at the ends of long bones

Bones within the limb form by endochondrial ossification (begins Carnegie stage 18) throughout embryo. This process is the replacement of cartilage with bone (week 5-12).

Osteoblasts manufacture bone and are derived from mesodermal in origin, arising from multipotential mesenchymal cells and further differentiate into bone-lining cells and osteocytes

Osteoclasts resorb bone and are derived from hematopoietic precursor cells formed by the fusion of monocytic cells at the bone sites to be resorbed.

The marrow of bones is the site of haematopoiesis, the generation of blood cells. At birth nearly all bones are a source of blood cells this is restricted with postnatal development to a few specific bones. Pluripotential stem cells reside in the marrow and are a self renewing source of stem cells or commitment to a progenitor cell.

The transcription factor Core Binding Factor 1 (Cbfa1) plays an essential role in osteoblast differentiation, bone formation, matrix production and mineralization

The organic matrix of bone consists of:

• 95% Type I collagen
• 5% proteoglycans and noncollagenous proteins (osteopontin and osteocalcin).

UNSW Embryology

Intramembranous formation

1. During this type of bone formaton mesenchymal cells migrate to the site of eventual bone formation
2. The cells condense, align and secrete an organic framework of extracellular matrix (ECM), i.e. the osteoid (or ground substance)
3. It should be noted that the cells continue to proliferate during the entire osteogenic process and all cells involved in bone formation retain this ability
4. The osteoid is laid down in longstrands
5. Osteoblasts (differentiated mesenchymal cells) line the osteoid and begin to deposit calcium salts, mineraliztion, forming the bone matrix
6. The bone matrix is a mixture of organic ECM and the inorganic salt components of the developing bone (the inorganic component is often analogized to the concrete portion of a building foundation and the organic portion to steel reinforcement within the concrete)
7. Together the two components give strength, some flexibility and the ability to hold a defined structure
8. Once the organic strands are mineralized they are termed trabecula (latin: little beam)
9. Lamella are consecutive growth rings added to the trabecula to increase thickness
10. The lamella are added onto by the mesenchymal cells and osteoblasts by cycles of osteoid secretion and mineraliztion (appositional growth) (this might be viewed as stalactites and stalagmites forming within a cave; whereby, consecutive layers of minerals are added to these structures and eventually they may join to form a complex network of mineralized supports)
11. When multiple trabecula within the developing bone contact one another a lattice structure forms
12. Areas of bones may completely fill-in with mineralized osteoid
13. Bones that does not completely fill-in and contain lattice structures are called primary cancellous bones
14. Bones that fill-in are called compact bones
15. Most, not all, bones are mixtures containing a compact outer surface surface and a cancellous interior

osteoclasts

Endochondral

1. Mesenchymal cells migrate to the site of eventual bone formation
2. The cells are induced to become chondrocytes
3. Chondrocytes are round cells, even in vitro
4. Chondrocytes proliferate into a very dense mass of cells devoid of blood vessels, i.e. cartilage
5. Cartilage forms in the shape of the ensuing bone
6. Chondrocytes secrete ECM containing primarily collagen and mucopolysaccharides
7. The ECM is at first a loose matrix
8. With continued EMC secretion, chondrocytes are forced apart and the cartilage grows (interstitial Growth)
9. The chondrocytes become encapsulated, the ECM thickens
10. Due to the physical entrapment, of the chondrocytes within the ECM, cell proliferation decreases within the matrix
11. The cartilage is also surrounded by layer of connective tissue cells also derived from mesenchyme (perichondrium)
12. The mesenchymal cells of the perichondrium also secrete ECM and add to cartilage by adding more layers (appositional growth)
13. Within the body of cartilage the encapsulated cells die and the matrix erodes
14. At this point, the cartilage is then replaced with bone
15. There is an invasion of blood vessels into the cartilage which bring in additional cell types
16. Invasion is a sign of impending bone development
17. Thus, the cartilage which was once avascular is now vascularized
18. The outer layer of mesenchyme cells which support apppostional growth over areas replaced with bone is now called the periosteum
19. The periosteum is identical to the perichondrium except for its location
20. As the cartilage is degraded, strands of remaining cartilage act as templates for osteoblasts
21. Osteoblasts secrete additional ECM which is subsequently calcified
22. Hence there are strands of calcified bone, trabecula, formed by this process also
23. Trabecula extend by appositional growth via the osteoblasts, trabecula also fuse
24. Areas of bone not completely filled in are cancellous
25. Areas filled in a compact
26. Most, not all, bones are mixtures containing a compact outer surface surface and a cancellous interior

General Classifications of Bones

1. Long Bones -- "longer than they are wide:" clavicle, humerus, radius, ulna, femur, tibia, fibula, metatarsals, metacarpals. Purpose: provide support and serve as  the interconnected set of levers and linkages that allow us to create movement. (formed from hyaline/articular cartilage)
2. Short Bones: carpals and tarsals: consist mainly spongy bone covered with a thin layer of compact bone. Purpose: allow movement, provide elasticity, flexibility, & shock absorption.
3. Flat Bones:  ribs, sternum and scapula. Purpose: protect and provide attachment sites for muscles.
4. Irregular Bones:  skull, pelvis, and vertebrae. Purposes:  support weight, dissipate loads, protect the spinal cord, contribute to movement and provide sites for muscle attachment.
5. Sesamoid Bones: a short bone embedded within a tendon or joint capsule, i.e. patella. Purpose: alter the angle of insertion of the muscle.

A typical synovial joint, seen at right, has four main featues:

1. joint capsule -  the joint enclosure, reinforced by and strengthened with ligaments
2. synovial membrane -  a continuous sheet of connective tissue lining the capsule; its cells produce synovial fluid that lubricates the joint and prevents the two cartilage caps on the bones from rubbing together
3. synovial fluid - produced by the synovial membrane, the fluid lubricates the joint. In the normal joint, very little fluid (less than 5cc) exists in the cavity.
4. hyaline (articular) cartilage - where the bones actually "meet"

Graphics modified from: The InnerBody: Anatomy Tutorials - Skeletal System
(Front View)	(Back View)

The skeleton has two main parts: the axial skeleton and the appendicular skeleton. The axial skeleton consists of the skull, the spine, the ribs and the sternum (breastbone) and includes 80 bones. The appendicular skeleton, consisting of 126 bones,  includes two limb girdles (the shoulders and pelvis) and their attached limb bones. 

Axial Skeleton (80 bones)

• skull - consiting of 1) the cranium (which encloses and protects the brain) and 2) the facial skeleton. The upper teeth are embedded in the maxilla; the lower teeth, in the mandible.
• mandible (jaw) - the only freely movable bone of the skull
• ribs, sternum (breastbone) - comprising  the "thorax"/thoracic cage, protecting the heart and lungs
• vertebral column - the "spine" 

The vertebral column (illustrated below and to the left)  transmits the body weight from the head, throax, and abdomen to the lower extremities and encloses and protects the spinal cord. Each vertebra has essentially the same basic components, with some variation based on location and allowed movements.

The vertebral body and the neural arch encircle the vertebral foramen. Stacked one on top of the other, these foramina form the vertebral canal, where the spinal cord resides.

Several structures strengthen the attachments between vertebrae: 1) anterior longitudinal ligaments in front of vertebral bodies and discs; and 2) posterior longitudinal ligaments behind bodies and discs; 3) the compact bone of the disc itself; 4) the interlocking hyaline cartilage surfaces of the neural arch joints; and 5) the ligaments attaching spinous processes to transverse processes.The intervertebral discs provide shock absorption.

Anterior Skull Lateral  Skull Vertebral Column

The orientation of the neural arch joints determines allowable motions: 1) the cervical spine () to rotate, flex forward, flex sideways, and extend backward; 2) the thoracic spine () to rotate; and 3) the lumbar spine () to flex forward, flex sideways, and extend backward. The sacrum () has a dual character, being part of both the vertebral column and pelvis. As such, it transmits the upper body weight to the lower exterminites.

Appendicular skeleton (126 bones, 64 in the shoulders and upper limbs and 62 in the pelvis and lower limbs)

• Upper Extremity - The arms (humerus - upper arm bone) are ultimately attached to the thorax,  via synovial joints, at the collarbone (clavicle) and shoulder bone (scapula) (shoulder joint). The scapula is attached to the thoracic cage only by muscles.  The elbow joint unites the humerus with the two lower arm bones - the ulna and radius. Three sets of joints connect the radius and ulna to the bones of the palm (metacarpals), via the eight small wrist carpals. Further, the knuckles (metacarpophalangeal, or MCP, joints) connect the metacarpals to the proximal phalanx of the fingers. Each finger has 3 phalanges (proximal, middle, distal), except the thumb which has only two.
  • shoulder/ scapula
  • arm and forearm, elbow
  • hand
• Lower Extremity - The pelvis transmits the upper body weight from the sacrum (at the sacroiliac joint) to the legs. It begins as 3 hip bones (ilium, ischium, and pubis) which fuse together when growth is completed. The hip joint unites the pelvis to the thigh bone (femur); the knee joint, which includes the knee cap (patella), links the femur to the lower leg bones - the tibia and fibula. The ankle joint links the lower leg bones to the talus. The body weight is then transmitted to the heel (calcaneous) and to the balls of the feet via the tarsal and metatarsal foot bones. The toes have a phalangeal structure like the fingers.
  • pelvic girdle
  • thigh and leg. knee, 
  • foot/ankle/toe

• Upper Extremity  
  • Shoulder 
  • Elbow & Forearm 
  • Wrist 
  • Hand 
• Spine 
  • Cervical & Lumbar Spine 

• Lower Extremity 
  • Pelvis and Hip 
  • Knee 
  • Ankle 

From

Impingement

Repeated overhead movements can squeeze and inflame your rotator cuff and bursa. Through the arthroscope, the doctor may see torn or swollen soft tissue of abnormal bone formations. I had the swollen soft tissue. Surgery helped clear space within my joint. Dr Springmeyer at the Highland Clinic in Shreveport performed the arthroscopic surgery. He removed the thickened bursa and trimmed the acromion bone to open up space.

Fibroblast growth factor (FGF)

FGFs are competence factors. They stimulate most of the cells involved in bone formation to enter the cell cycle. FGF is a competence factor for most cells of mesenchymal origin.

As shown above, FGF4 and FGF8 are intricately involved in limb bud formation. The stimulate proliferation of mesenchymal cell beneath the AER. Since this growth factor will stimulate the proliferation of most mesenchymal cells its effects are controlled by site specific expression. This is illustrated by induction of its initial expression only in the region of intermediate mesoderm where cells must proliferate rapidly to form the limb bud.

FGF begins the cascade of gene expression necessary for cell proliferation, ex. cyclin.

Insulin-like growth factors I and II (IGF-I and IGF-II)

The IGFs cause hypertrophy of cells (or tissues), i.e. they are progression factors. The IGFs are made by all fetal and embryonic tissues in a constituitive manner and therefore IGFs are always present during osteogeneis. This is not the case during postnatal growth whereby IGF expression varies from tissue to tissue and expression is highly regulated.

Cells that enlarge have two fates:

• Cells can enlarge and stay large: ex. hypertrophic chondrocytes at the epiphyseal plate: this also includes tissue enlargement (i.e. interstitial growth - collagen synthesis, proteoglycan synthesis; increased bone mineralization)
• Cells must enlarge to divide to ensure that the daughter cells are roughly the same size as the mother cell: this cell hypertrophy includes enhanced protein, RNA and DNA synthesis.

The IGFs cause hypertrophy of all cells involved in osteogenesis.

The ultimate question: If IGFs are present and they enlarge how do they know whether to stay large or divide? Of course if competence factors are present the cells enther S phase and then the progression factors drive cells through the cell cycle. If competent factors are absent then cells enlarge and stay large.

Remember what S stands for: synthesis. Progression factors are needed for cell proliferation because the stimulate synthesis of everything that must be made in the S-phase of the cell cycle, including DNA.

  Interleukin (IL)-6

IL-6 is an example of a morphogen involved in osteoclast differentiation.

This morphogen induces monocyte differentiation into osteoclasts and is involved in several of the other steps up to monocyte formation.

In most cases cells will proliferate when presented with a single competence and a single progression factor. In most cases the differentiation of a cell type involves several steps requiring several morphogens.

Bone morphogenic proteins (BMP)

This name identifies a number of morhpogens related in structure to transforming growth factor (TGF)-ß1 & 2 including:

• BMP - 2
• BMP - 3
• BMP - 4
• BMP - 5
• BMP - 6
• BMP - 7
• dpp (Decapentapeptide) drosophila body patterning
• Vg1 Xenopus body patterning

BMPs have osteoinductive activity i.e., BMP can induce mesenchymal cells to become bone cells (chondrocytes and osteoblasts)

BMPs act synergistically with retinoic acid

shh induces BMP expression in the developing limb bud

http://classes.aces.uiuc.edu/AnSci312/Bone/Bonelect.htm