Bone Tissue ISU MED 1 – 2022

Asst. Prof. Dr. Hakan DARICI

Bone as an organ Bone as a tissue
• Bone tissue • Cells
• Other connective • Extracellular matrix
tissues: • Fibers
• Blood tissue, • Ground substance
• Hemotopoietic tissue,
• Adipose tissue
• Cartilage tissue
• Nerve tissue
According to shape
1. Long bones
• Diaphysis (middle part)
• Metaphysis
• Epiphysis (ends)
2. Short bones
3. Flat bones
4. Irregular bones
According to maturity
1. Immature bones
• In fetuses and adult mouth area
• Nonlamellar
• Less mineralized
• More cells, less ECM
2. Mature bones
• Concentric lamellae system
• Osteon structure
• Haversian and Volkmann’s canals
Differences

Homogen Osteon structures Trabecullar

Immature bone Mature bone
 Zones of the Bone
1. Periosteum
2. Compact bone
3. Spongy bone
4. Endosteum
Zones of the Bone
1- Periosteum:
• Connective tissue that covers the bone.
• Outer part of it is dense connective tissue.
• Inner part is more cellular. There are osteoprogenitor cells.
• There is no periosteum at the joint areas.
• Collagen fibers are parallel to bone surface and produce a
capsule.
• At the tendon and ligament areas, collagen fibers extends from
the surface at an angle → Sharpey Fibers
Zones of the Bone

2- Compact bone
• Osteon structure (Haversian systems)
• Interstitial lamellae

3- Spongy bone
• Trabecule and spicules
 Zones of the Bone
4- Endosteum:
• Layer that covers surfaces of the bone marrow
and trabecules
• Usually, it consists of osteoprogenitor cells and
osteoblasts

5- Bone marrow:
• Where the blood is formed in adults
• Types of bone marrow: Red (active) and yellow (lots of adipose tissue) BM
• Red BM: Long bones, sternum, iliac crest areas
• In excessive blood loss cases, Yellow BM → Red BM
1. Cells
• Osteoprogenitor cells,
• Osteoblasts,
• Osteocytes,
• Osteoclasts.

2. Fibers
• Collagen type I

3. Kemik Matriksi
• Proteoglycans  GAGs
• Glycoproteins → Osteonectin, osteopontin
• Bone-specific proteins → Osteocalcin, protein S
• Growth factors and cytokines: IGF, TGF-b, BMPs (especially BMP-2 and BMP-7)
 Fibres
• 90% of bone matrix is collagen
• Mostly collagen type I
• Additionally collagen type V

• Both collagen fibers and ground substance are calcified with calcium phosphate
compound called hydroxyapatite crystals
Bone Matrix
1. Proteoglycans, GAGs

2. Multiadhesive Glycoproteins
• Osteonectin: Connects collagens to hydroxyapatite crystals

• Sialoproteins (Osteopontin/BSP1): Cell-bone matrix connection

• Bone Sialoprotein 2 (BSP2): Initiates calcium phosphate formation

3. Bone-specific vitamin K-dependent proteins

• Osteocalcin: Grabs calsium at the blood

• Protein S, matrix Gla-protein….

4. Growth factors and Cytokines

• IGF, TGF-b, PDGF

• Bone Morfogenic Proteins (BMP) (Esp. BMP-7): Trigger bone formation

 Bone Cells Mesenchymal Stem Cells

• Osteoprogenitor cells
• Osteoblasts / osteocytes
• Bone-lining cells (periosteal/endosteal cells)
Osteoprogenitor Cells
• Osteoclasts

Osteoblasts

Osteocytes
Osteoblasts
• They are differentiated from osteoprogenitor cells.
• They are found at the bone surface and newly formed-bone areas at the wall of
the resorption cavity.
• Cubic or poligonal shaped cells. They can be shown with osteocalcin.
• 5% of all bone cells.
• They initiates mineralization, synthesize matrix.
• They are controlled through RANKL* and Parathormon receptors.
• Livetime: ~12 days

*RANKL: Receptor Activator of Nuclear Factor kappa-B Ligand

 Osteocytes
• They are differentiated from osteoblasts.
• They are found at the spaces in the bone matrix which is called
lacunae.
• Small oval, pale colored cells. There are extensions that is called
canaliculus.
• 95% of all bone cells.
• They protect bone matrix, maintain Ca and P homeostasis.
• They can detect mechanical stress.
• They are controlled through RANKL and Parathormon receptors like
osteoblasts.
• Lifetime: 10-20 years
Bone marrow 1000X
Osteocyte 4000X magnification
 Osteoclasts
• They are differentiated from Hematopoietic stem cells (CFU-GM).
• They are found at the bone surface and destruction areas of the resoption cavity.
• Big cells with multiple nuclei. They are observed as settled in Howship lacunae.
• 1% of all bone cells.
• They can be shown with RANK* and MMP-9 immunostaining or TRAP** method.
• They are controlled through RANKL, calcitonin, and Parathormon receptors.
• Lifetime: ~3 days

*RANK: Receptor Activator of Nuclear Factor kappa-B

**TRAP: Tartarate Resistant Acid Phosphatase
 Osteoprogenitor

Osteoprogenitor

Osteoclast

Osteoprogenitor
Osteoblast
Osteoblast

Osteocyte

Osteocyte

Osteoblast
 Resorption cavity
Remodelling
Control of the Bone Formation and Destruction
Parathormon (PTH):
• If the Ca level decreases in blood → secreted from Parathyroid gland.
• Stimulate osteocytes and osteoclasts → Bone destruction → Ca released

Calcitonin:
• If the Ca level increases → secreted from Thyroid gland
• Remove the effect of PTH → Bone formation
Other Bone-Related Hormones
Growth Hormon
Insulin and Insulin-like Growth Factor-I (IGF-I)
Thyroid Hormones
→ Stimulate epiphysis cartilage and osteoprogenitor cells to proliferate.

Insufficient GH → Hypophysical dwarfism

Excessive GH (infancy and childhood) → Gigantism
Excessive GH (adulthood)→Excessive growth of bone surfaces →Acromegaly
 Effects of Vitamins and Minerals to the Bone
• Calsium deficiency (childhood) → Rickettsia
Insufficient Ca intake or Vitamin D (have role in Ca intake) deficiency

• Calsium deficiency (adulthood) → Osteomalacia

• Vitamin C deficiency → Problem with collagen synthesis → Scurvy

• Vitamin A deficiency → Endochondral ossification stops

Vitamin A excess → Fragile bones
Bone Fractures
Fracture Recovery Stages:

1. Hematoma formation
2. Inflammation (1 week)
3. Granulation tissue (callus)
Type II and III collagen. Loose connective
tissue. (2-3 weeks)
4. Fibrous cartilage formation at
callus
5. Bone callus replaces soft callus
(3-4 months)
6. Remodelling (several
months/years)
 Osteoporosis

• Porosis (holey) bone. Bone destruction > Bone formation

• Osteoclast activity is controlled by PTH and partially IL-1 and TNF. Estrogen inhibits them.
• Osteoporosis Type I: Menopause → Low E2 → High osteoclast activity → Osteoporosis
• Osteoporosis Type II: After 70-80 years old
• Seconder osteoporosis: Drug treatment (corticosteroids), malnutrition, immobility, prolonged stay in the weightless
environment, after metabolic diseases (hyperparathyroidism)
• E2 and progesterone drugs, synthetic PTH, exercise are effective aganist osteoporosis.
In Space & Mars