basic concept on cellular and acellular component of bone

1. Cellular and Acellular
components of bone:
Dr. Kshitiz Gyanwali
FCPS resident in Orthopedic surgery
B & B Hospital, Gwarko , lalitpur

2. Introduction:
 human skeletal system consists of 206 bones.
 Body has to deal with great physical stress,
predisposing it to injuries and disorders.
 with minimal clinical intervention, simple fractured
bones can heal into functionally normal bone.

3. Bone:
 Normal bone is lamellar and can be cortical or cancellous.
 Immature and pathologic bone is woven, is more random with more
osteocytes.
 Histology of bone:
1. Type:
- cortical and cancellous
2. Cell biology:
- osteoblasts, osteocytes, osteoclasts

4. 1. Cortical bones:
-Makes up 80% of the skeleton and is composed of tightly packed osteons
or haversian systems connected by haversian canals.
- canals contain arterioles, venules, capillaries,nerves, and possibly
lymphatic channels
- Osteons lie in between the interstitial lamella.

5. Contd..
- Nutrition is via intraosseous circulation
- slow turnover rate
- Higher resistance to torsion and bending

6. Histology of cortical bone:

7. 2. Cancellous bone:
 Less dense and undergoes more remodeling according to lines of stress(Wolff’s law)
 higher turnover rate
 More elastic than cortical bone.

8. Histology of cancellous bone:

9. Cell biology:
A. Osteoprogenitor cells:
-These local mesenchymal cells line haversian canals, endosteum, and
periosteum.
-awaits for the stimulus to differentiate into osteoblasts.

10. B. Osteoblasts:
- Derived from undifferentiated mesenchymal cells.
-These cells have more endoplasmic reticulum, Golgi apparatus,
and mitochondria
- More differentiated, metabolically active cells line bone surfaces
while less active cells lie in "resting regions“.

11. Contd..
 Activation occurs due to disruption in the lining cell layer.
 Cell differentiation is affected by:
- interleukins, platelet derived growth factor (PDGF), and insulin derived
growth factor (IDGF)
 Produce type I collagen
 High Alkaline Phosphatase activity

12.  Receptor-effector interactions:
1. PTH
2. 1,25-dihydroxyvitamin D
3. Glucocorticoids
4. Prostaglandins
5. Estrogen

13. Clinical implications:
 High level of serum ALP indicates osteoblastic overactivity:
- Metastatic disease of bone
- Healing Fracture
- Osteosarcoma
- Acromegaly

14. Cellular differentiation and synthesis:

15. C. Osteocytes:
 Make up 90% of the cells in the mature skeleton and serve to maintain bone.
 Derived from osteoblasts.
 Not as active in matrix production as osteoblasts.
 Controls extracellular concentration of calcium and phosphorus by:
1. Resorption: hypocalcemic states
2. Deposition: physical activity, exertion
 stimulated by calcitonin and inhibited by PTH

16. Clinical implications:
 premature death or dysfunction of osteocytes :
- Osteoporosis
- Osteoarthritis

17. D. Osteoclasts:
 Resorbs bone.
 Multinucleated, irregularly shaped giant cells
 Possess a ruffled ("brush") border
 Originates from hematopoietic tissues (monocyte progenitors from giant cells)
 Binds to bone surface via cell attachment proteins(integrins)

18.  synthesize tartrate-resistant acid phosphatase
 Produces H+ ions,lowers PH and increases the solubility of hydroxyapatite
crystals
 Organic matrix is digested by proteolytic action.
 Bone resorption seen in Multiple myeloma, metastatic bone diseases
 IL-1: stimulator of osteoclastic activity
 IL-10: suppressor of osteoclast formation

19. Matrix of bone:
 Consists of:
1. Organic: 40% of the dry weight of bone
2. Inorganic components: 60% of the dry weight of bone

20. 1.Organic/Cellular components:
A. Collagen:
-responsible for tensile strength of bone
-90% of the organic matrix of bone :composed primarily of type I(one) collagen
- triple helix of two alpha-1, and one alpha-2 chains that are quarter-staggered to
produce a collagen fibril

21. Hole zones and pores:
 Hole zones (gaps) exist within the collagen fibril
between the ends of molecules.
 Pores exist between the sides of parallel
molecules.
 Mineral deposition (calcification) occurs within
these hole zones and pores.

22. B. Proteoglycans:
-responsible for the compressive strength of bone
-they inhibit mineralization.
-Composed of glycosaminoglyan (GAG)-protein complexes

23. Glycosaminoglycans (GAGs):
present in all tissues, in the extracellular matrix, and on the surface of every cell
Various form:
- heparin/heparan sulfate: - role in cell signaling pathway
- chondroitin sulfate (CS)/dermatan sulfate: - delivers nutrition to joint cartilage,
- speeds formation of new joint cartilage
- keratin sulfate (KS): - maintain tissue hydration (bone and cartilage)
- hyaluronic acid: - lubricates joint

24. C. Matrix Proteins (Non collagenous):
- Promote mineralization and bone formation
a.Osteocalcin:
- attracts osteoclasts and is directly related to the regulation of bone density
- most abundant
- level increased in Paget's disease, renal osteodystrophy and
hyperparathyroidism.

25. B. Osteonectin :
- secreted by platelets and osteoblasts
- responsible in regulation of calcium or the organization of mineral
within the matrix
C: Growth Factors and Cytokines:
- present in small amount in matrix
- Transforming growth factor beta(TGF-13)
- Insulin-like growth factor(IGF)
- Interleukins (IL-I , IL-6)
- Bone morphogenic proteins

26. Inorganic/Acellular Components:
A. Calcium Hydroxyapatite (Ca10(P04)6(OH)2):
-Provides compressive strength of bone.
- Makes up most of the inorganic matrix
- Responsible for the mineralization of the matrix.
- Primary mineralization occurs in gaps (holes and pores) in the collagen
- Secondary mineralization occurs on the periphery.

27. B. Osteocalcium Phosphate (Brushite):
-Makes up the remaining inorganic matrix

28. Dissecting Bone at the Tissue Level:
1. Periosteum:
- Dense bilayer membrane, responsible for appositional bone
growth.
a. outer fibrous layer : providing structural support
b. inner cambium layer: abundant in osteoprogenitor cells

29. 2. Osseous Tissue
1. enveloped between the periosteum and the
endosteum
a. Cellular components: collagen fibers
b. Acellular components: hydroxyapatite

30. 3. Endosteum
• Endosteum are arranged in a mosaic pattern of:
-formative: active osteoblasts
-resting: preosteoblasts
-resorptive: osteoclasts

31. Remodeling of bone:
 Removal of external stresses can lead to significant bone loss,
 Can be reversed back upon remobilization.
1. Cortical Bone:
- Remodels by osteoclastic tunneling (cutting cones)
- followed by layering of osteoblasts and successive deposition of layers of lamellae
-osteoclasts: bore holes through hard cortical bone
- osteoblasts: lay down osteoid to fill the resorption cavity

32.  Cancellous Bone:
-Remodels by osteoclastic resorption, followed by osteoblast, which lay
down new bone.
- layers of lamella is not formed

33. 4. Bone Marrow
 vulnerable soft tissues that is protected inside bone
 Research has proved for its use in bone regeneration.
 Kuznetsov SA, Krebsbach PH, Satomura K, Kerr J, Riminucci M, Benayahu D,
Robey PG
 J Bone Miner Res. 1997 Sep; 12(9):1335-47.
 Conclusion:
 The stromal fibroblast cells isolated from human bone marrow could differentiate into
osteoblasts, and form bone when subcutaneously implanted into immunodeficient mice.

34. Concept of tissue engineering:
1. Discovery of bone morphogenetic proteins (BMPs) in 1965.
2. Discovery of mesenchymal stem cells (MSCs) in 1991
3. Development of materials mimicking bone extracellular matrix

35. Summary:
 Cellular and acellular components are the integral part of complex bone.
 Understanding about these components help us to deal with associated
pathologies.
 More detail and thorough study is still necessary at the cellular level for
advanced tissue engineering techniques.