Growth and Development of Bone

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					Growth and Development of
  Fall 2006
 l   Bone (Latin: "os") is a type of hard endoskeletal
     connective tissue found in many vertebrate animals.
     Bone is the main tissue of body organs; organs that
     support body structures, protect internal organs, (in
     conjunction with muscles) facilitate movement; and are
     involved with cell formation, calcium metabolism, and
     mineral storage. The bones of an animal are,
     collectively, known as the skeleton. Bone has a
     different composition than cartilage, and both are
     derived from mesoderm. In common parlance,
     cartilage can also be called "bone", certainly when
     referring to animals that only have cartilage as hard
     connective tissue

 l Bone   is a relatively hard and lightweight
   composite material, formed mostly of
   calcium phosphate
 l Bone can be either compact or
   cancellous (spongy). Cortical (outer
   layer) bone is compact
 l Cortical bone accounts for 80% of the
   total bone mass of the adult skeleton

 l   Long bones are tubular in structure (e.g. the
     tibia). The central shaft of a long bone is called
     the diaphysis, and has a hollow middle—the
     medullary cavity filled with bone marrow.
     Surrounding the medullary cavity is a thin layer
     of cancellous bone that also contains marrow.
     The extremities of the bone are called the
     epiphyses and are mostly cancellous bone
     covered by a relatively thin layer of compact
 l   Short bones (e.g. finger bones) have a similar
     structure to long bones, except that they are shorter.
 l   Flat bones (e.g. the skull and ribs) consist of two
     layers of compact bone with a zone of cancellous
     bone sandwiched between them.
 l   Irregular bones are bones which do not conform to any
     of the previous forms (e.g. vertebrae).
 l   All bones consist of living cells embedded in a
     mineralised organic matrix that makes up the main
     bone material
Bone cells

 l Osteoblasts   are typically viewed as
   bone forming cells. They are located
   near to the surface of bone and their
   functions are to make osteoid and
   manufacture hormones, such as
   prostaglandins, which act on bone itself.
Bone cells
 l   Osteocytes originate from osteoblasts which have
     migrated into and become trapped and surrounded by
     bone matrix which they themselves produce.

 l   The space which they occupy is known as a lacuna.

 l   Their functions include to varying degrees: formation
     of bone, matrix maintenance and calcium

 l   They possibly act as mechano-sensory receptors—
     regulating the bones' response to stress.
Bone cells
 l   Osteoclasts are the cells responsible for bone
     resorption. Osteoclasts are large, multinucleated cells
     located on bone surfaces in what are called Howship's
 l   The process of bone resorption releases stored
     calcium into the systemic circulation and is an
     important process in regulating calcium balance. As
     bone formation actively fixes circulating calcium in its
     mineral form, resorption actively unfixes it thereby
     increasing circulating calcium levels. These processes
     occur in tandem at site-specific locations and are
     known as bone turnover or remodeling. Osteoblasts
     and osteoclasts, coupled together via paracrine cell
     signalling, are referred to as bone remodeling units.
Origin of Bone cells

 l   Osteogenesis
     l   Endochondral ossification
          l   Requires a cartilaginous template
     l   Intramembranous ossification
          l   Lack of cartilaginous template
 l   Axial Skeleton
     l   Formed from sclerotome cells
 l   Appendicular Skeleton
     l   Formed from cells derived from the lateral plate
Origin of cells

 l Osteoblasts  come from mesenchymal
   cells and are directly involved in the
   bone matrix production
 l Osteocytes are mature osteoblasts are
   responsible for maintenance of the bone
    l   In adult bone, osteocytes out number
Origin of cells

 l Chondroblasts-   form cartilage which is
   associated with bone required for bone
 l Osteoclasts are involved in bone
   resorption (breakdown) and remodeling.
   The number in adults is small
 l Bone lining cells – inactive cells found on
   the surface of the bone and may used as
   precursors for osteoblasts

 l Tendons- connective tissue that
   connects muscle to bone
 l Ligaments – connective tissue that
   connects bone to bone
Endochondral Ossification
 l   Occurs with the replacement of cartilage with
 l   Both axial and appendicular skeletons develop
     cartilaginous structures prenatally and serves
     as a template for ossification
 l   The cartilagenous matrix near the shaft of the
     bone begins to calcify as chondrocytes mature
     and enlarge
 l   This calcification prevents nutrients from
     reaching the chondrocytes, thus they die, thus
     preventing new growth (ossification)
Endochondral Ossification

 l The  perchondrium is converted into
   periosteum and ostioblasts become
   apparent in the inner layer of the
   periosteum. These form a layer of bone
   around the diaphysis.
 l Primary ossification center is established
   in the central portion of the shaft as a
   result of capillaries and osteblasts that
   migrate into that region
Endochondral Ossification

 l   The calcified cartilage matrix in the center is
     broken down and action of the osteoblasts
     replaces the cartilage with new bone
 l   Bone is formed from the center of ossification
     until the entire diaphysis is filled with spongy
 l   As the bone grows, osteoclasts increase the
     inside diameter of the hollow central protion of
     the diaphysis so that the marrow cavity results
Endochondral Ossification

 l Secondary   center of ossification occurs
   at each epiphysis
 l Osteoblasts in this area produce spongy
   bone that replaces the cartilage at the
 l A thin layer of articular cartilage to
   reduce the friction at joints (bone to
Endochondral Ossification

 l The  epiphyseal plate or growth plate is a
   thin region of cartilage between the
   diaphysis and epiphysis of long bones
 l Increased length of long bones involves
   action of both chondrocytes and
   osteoblasts at the growth plate
 l The chondrocytes closest to the
   epiphyseal side of the growth plate are a
   part of the reserve zone (stem cell zone)
Endochondral Ossification

 l   Proliferating chondrocytes produce
     extracellular matrix such as collagens and
 l   Mature chondrocytes eventually die and leave
     behind a calcified matrix which is replaced with
     bone via invading capillaries and osteoblasts
 l   Chondroosseous junction is the region of
     growth between the cartilage and new bone
Endochondral Ossification

 l Degradation   of the growth plate cartilage
   is important in allowing bone formation to
   occur at a normal rate
 l Growth plate turnover is the rate at
   which the condrocytes progress through
   the varying zones
Termination of long bone growth

 l The   diaphysis of long bone will continue
   to lengthen as long as the rate of
   cartilage growth remains faster than the
   rate of osteoblast invasion at the growth
   plate – as long as it does not ossify
 l Cartilage growth stops or slows to a rate
   that allows it to be overcome with
   ossification – epiphyseal closure
Termination of long bone growth

 l Break  joint in sheep – separation is at
   the distal end of the epiphyseal plate of
   the metacarpal bone
 l The distal end of the metacarpus is
   referred to as the spool joint
Intramembranous ossification

 l Increases   in diameter of growing bone
   through appositional growth
 l Osteoblasts that differentiate from the
   periosteum deposit new bone matrix
   within the periosteum
 l Osteoblast activity is highest for those
   cells that surround the periosteal blood
Intramembranous ossification

 l New  osteons are produced as a result of
   the concentric deposition of bone that
   results from the action of osteoblasts
   and the formation of osteocytes
 l These new osteons contribute to
   compact bone and increase the overall
   outside diameter of the bone
Bone Resorption

 l   While osteoblasts and osteocytes are adding
     new bone to the outer surface, osteoclasts are
     removing bone at th einner surface and
     enlarging the marrow cavity
 l   Osteoclasts make contact with the bone
     through a region referred to as ruffled border
     and subsequently have the ability to degrade
     both inorganic and organic matrices of the
Bone Resorption
 l   The degradation of the inorganic matrix is
     accomplished by solubilization of crystalline
     hydroxapatite crystals.
 l   Osteoclasts appear to be capable of creating an acidic
 l   The resulting decrease in pH in the local region is key
     to the solubilization process
 l   This process results in the mobilization of minerals
 l   Degradation of the organic matrix is accomplished with
     enzymes, including collagenase and proteinases
Bone Resorption

 l Types   of marrow
   l Red marrow – chief blood cell forming organ
     of the adult and is found in spongy bone of
     the epiphysis of long bones and main
     bodies of ribs, sternum and vertebrae
   l Yellow marrow – composed mainly of
     adipose tissue and found in the medullary
     cavity of bones
Bone Remodeling

 l Osteoblasts  form osteons (basic
   functional unit of compact bone) by
   osteogenesis whereas osteoclasts
   destroy osteons by resorption.
 l The balance between these two yields
   net bone deposition
 l As animals age, bone resorption may
   exceed formation and bone mass
Bone Remodeling
 l   Bone remodeling provides a mechanism for
     bone to adapt to new stresses especially
     heavily stressed bone that actually helps it
     become stronger
 l   Remodeling is initiated through osteoclast
     activation to removal of bone matrix and is
     followed by osteoblast formation for the
     production of new bone.
 l   Osteoblasts respond to the stress on bones
     and deposit additional bone in locations of
     stress to make bones stronger
Bone Remodeling

 l Increased force of muscles will result in
   increased bone growth where tendons
   connect to bones
 l The amount of stress is closely related to
   the degree of mineralization and porosity
Factors affecting bone growth and
 lA  lot of bone remodeling is a result of
   hormonal action.
 l Hormones involved in bone growth and
   remodeling is PTH and Calcitonin
 l Calcitonin is released by the thyroid
   gland that decreases osteoclasts
   yielding decreased mobilization of
   calcium from bone and decreasing blood
   calcium concentrations
Factors affecting bone growth and
 l   PTH acts on bone, kidney, and gastrointestinal
     tract to increase blood calcium
 l   Action on bone includes an increase in
     osteoclast activity
 l   This is mediated through signals from
     osteoblasts and osteocytes and often
     mobilization of calcium out of bone via
 l   Also, PTH regulates phosphorus metabolism
Factors affecting bone growth and
 l   Other hormones that regulate bone growth and
     remodeling are testosterone and estrogen
 l   Both estrogen and testosterone hasten
     ossification and have an effect on epiphyseal
 l   As a result, castration yields longer bones
     (longer, taller animals) because of slower
     closure processes
 l   Estrogens are more effective in mediating
     closure of the growth plate than testosterone,
     thus females are smaller statured than males

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