"Anatomy and Physiology of Bone"- Sheersha Pramanik

In my presentation, I have described about the anatomy and physiology of bone and also did a elaboration on the pathways which is responsible for bone cells formation. For more details related to bone you can contact me on my email : [email protected]

1. ANATOMY OF BONE presented by: SHEERSHA PRAMANIK(NIPERA1719MD10) COURSE INSTRUCTOR: Dr. Akshay Srivastava

2. BONE – AN INTRODUCTION A  bone  is a rigid organ that constitutes part of the vertebrate skeleton. There are around 270 to 300+ bones in Infants which gets reduced to 206 bones in adults. Bones are dynamic structures that are undergoing constant change and remodelling in response to the ever-changing environment.  Bones support and protect the various organs of the body, produce  red and  white blood cells, store minerals, provide structure and support for the body, and enable mobility. It has a  honeycomb-like matrix internally , which helps to give the bone rigidity . The largest bone in the body is the  femur or thigh-bone, and the smallest is the  stapes  in the middle ear.

3. CLASSIFICATION OF BONE According to position : Axial Skeleton = T he   axial skeleton  is the part of the skeleton  that consists of the  bones of the head and trunk of a  vertebrate . https ://en.wikipedia.org/wiki/Axial_skeleton

4. Contd. 2. Appendicular Skeleton : The appendicular skeleton is composed of the upper limbs, lower limbs, pectoral girdle, and pelvic girdle. The appendicular skeleton functions to anchor the limbs to the axial skeleton. https://en.wikipedia.org/wiki/Appendicular_skeleton

5. CONTD. 2. According to Size and Shape : Long bones – A. DIAPHYSIS: Portion of long bone between two cartilaginous ends. - Shaft of long bone. Consist of Adipose tissue and bone marrow. Consist of Nutrient Foramen directed away from the growing end. - Primary Ossification occurs in this region. https://en.wikipedia.org/wiki/Diaphysis

6. CONTD. B. EPIPHYSIS : The   epiphysis  is the rounded end of a long bone, at its  joint  with adjacent bone(s). Epiphyseal Line: The  epiphyseal plate   (   growth plate ) is a hyaline cartilage plate in the  metaphysis  at each end of a  long bone . It is the part o f a long bone where new bone growth takes place. E nds of epiphyses are covered with  hyaline cartilage(" articular cartilage "). C. METAPHYSIS : M etaphysis  is the narrow portion of a long bone between the  epiphysis and the diaphysis . It consists the growth plate. https ://en.wikipedia.org/wiki/Long_bone

7. EXAMPLES OF LONG BONE https://en.wikipedia.org/wiki/Long_bone

8. CONTD. Short Bones : Short bones  are those  bones that are as wide as they are long. Their primary function is to provide support and stability with little to no movement. https://en.wikipedia.org/wiki/Short_bone

9. CONTD. Flat bones : Flat bones  are  bones whose principal function is either extensive protection or the provision of broad surfaces for muscular attachment.  They are thin with parallel surface. Present between two compact bone. https://en.wikipedia.org/wiki/Flat_bone

10. CONTD. Irregular Bones : The  irregular bones  are bones which form their peculiar form. -Have complex shapes. Irregular bones serve various purposes in the body, such as protection of nervous tissue (such as the vertebrae protect the spinal cord ), and maintaining  pharynx and   trachea support , and  tongue attachment (such as the hyoid bone). https://en.wikipedia.org/wiki/Irregular_bone

11. CONTD. Pneumatic Bones : Certain irregular bones contain large air spaces lined by epithelium. - Make the skull light in weight, - Helps in resonance of voice. - Act as air conditioning chambers for the inspired air. Examples : Maxilla, Sphenoid etc . http ://infinitespider.com/pneumatic-bones-birds-and-you/

12. CONTD. Sesamoid Bones : It is the bone which is embedded within a tendon or muscle. S esamoids act like  pulleys, providing a smooth surface for tendons to slide over, increasing the tendon's ability to transmit muscular forces . https ://en.wikipedia.org/wiki/Sesamoid_bone

13. ALL IN ONE

14. STRUCTURAL CLASSIFICATION (Macroscopically) 1. Compact Bone : Cortical bone, also known as compact bone, forms the hard outer shell of all bones. It is the strongest and densest form of bone in the body.  - Strong dense (80% of the skeleton) - Best developed in the cortex of long bones - The functional unit is Osteon (Haversian System) which contains osteoblasts and arteriole supplying the osteon. OSTEONS : They are cylindrical, parallel to bone, and are group of hollow tube. Each osteon consists of concentric layers (Lamellae), of compact bone tissue that surround a central canal, the  Haversian canal . https://www.studyblue.com/notes/note/n/6-skeletal-system /deck/7962817 https://www.dreamstime.com/

15. Microscopically 1. HAVERSIAN CANAL : Haversian canals are a series of microscopic tubes in the outermost region of bone called cortical bone that allow blood vessels and nerves to travel through them . - Each Haversian canal generally contains one or two  capillaries and  nerve fibres. - The channels are formed by concentric layers called  lamellae. 2. LACUNAE : Small spaces between lamellae, each containing a bone cell. A lacuna never contains more than one osteocyte. Example : Sinuses https ://www.embibe.com/

16. CONTD. 3. LAMELLAE : Interstitial Lamellae : T he space between osteons is occupied by interstitial lamellae, which are the remnants of osteons that were partially resorbed during the process of bone remodelling. Concentric Lamellae : Thin plates of bony tissue consisting of ground substance or matrix of collagen fibres lying in a calcified material. They are arranged concentrically around the haversian canal. Circumferential Lamellae : Found at inner and outer periphery of cortex. http://studydroid.com

17. CONTD. 4. Bone Canaliculi : Bone canaliculi  are microscopic canals between the lacunae  of ossified  bone. - They are the fine radiating channels which connects lacunae with each other and Central Haversian Canal. -   Osteocytes do not entirely fill up the canaliculi. The remaining space is known as the  periosteocytic space, which is filled with periosteocytic fluid.    https://fatunmbi.wordpress.com http://antranik.org/cartilage-and-bones /

18. CONTD. 5. Volkmann's Canal : Volkmann's canals,  also known as perforating holes or channels, are atomic arrangements in cortical bones . - Oblique canals running at right angles to the long axis of the bone. - Contains the neurovascular bundle and connect Haversian canals with the medullary cavity and surface of the bone. http://slideplayer.com

19. CONTD. 6. Periosteum : The  periosteum  is a  membrane that covers the outer surface of all  bones  except at the joints of long bones. -  consists of dense irregular connective tissue. - Consists of two layers : a. Outer Fibrous layer (contain Firoblasts ) b. Inner Cambium layer ( Contains osteogenic cells) https://en.wikipedia.org/wiki/Periosteum

20. CONTD. 7. Endosteum :   E ndosteum  (plural endostea) is a thin vascular membrane of connective tissue that lines the inner surface of the bony tissue that forms the medullary cavity of long  bones. - To prevent the bone from becoming unnecessarily thick,  osteoclasts resorb the bone from the endosteal side. https://en.wikipedia.org/wiki/Endosteum

21. CANCELLOUS BONE It is the internal tissue of the skeletal bone and is an open cell  porous network. -  Cancellous bone has a higher surface-area-to-volume ratio than cortical bone because it is less dense. - This makes it softer, and weaker but more flexible. The greater surface area also makes it suitable for metabolic activities such as the exchange of calcium ions.  - Does not have osteons. -  The primary anatomical and functional unit of cancellous bone is the  trabecula. - Trabeculae has no blood vessels. https ://image.slidesharecdn.com

22. COMPOSITION OF BONE A. Organic matrix (25%) B. Inorganic Materials (65%) C. Water (10%) ORGANIC MATRIX BONE CELLS INTERCELLULAR MATRIX Mesenchymal precursor cells Osteogenic Cells Collagen Osteocyte Protein peptides Osteoblast Proteoglycans Osteoclast Lipids Bone lining cells

23. OSTEOPROGENITOR CELLS These are the mesenchymal stem cells (MSC) that divide to form osteoblasts in bone marrow.   Runx2 (which may also be known as Cbfa1), and Osx (a zinc finger containing transcription factor) are necessary for osteochondroprogenitor cells to differentiate into the osteoblast cell lineage.  Runx2 : Runt-related transcription factor 2  (RUNX2) also known as  core-binding factor subunit alpha-1  (CBF-alpha-1) is a protein that in humans is encoded by the  RUNX2  gene . OSX : Transcription factor Sp7,  also called Osterix (Osx), is a protein that in humans is encoded by the  SP7   gene. These cells are present in endosteum, periosteum, stromal component of Bone matrix.

24. CONTD. The pathways which are responsible for osteoblast differentiation are :

25. SIGNALLING PATHWAYS 1. WNT SIGNALLING : The  Wnt signaling pathways  are a group of  signal transduction pathways made of  proteins  that pass signals into a cell through cell surface receptors. The canonical pathway is responsible for the osteoblast differentiation. Accumulation of β -catenin in cytoplasm DSH becomes activated via phosphorylation and its DIX and PDZ domains inhibit the GSK3 activity of the destruction complex Act as transcriptional co- activator of transcription factors (TCF/LEF Fam) Axin becomes de-phosphorylated and its stability and levels decrease W NT causes the translocation of the negative WNT regulator , Axin WNT binds to FZ and its co receptor LRP 5/6 Accumulation of β- catenin in cytoplasm Translocation to the nucleus Act as a transcriptional co-activator Of transcription factors (TCF/LEF FAM)

26. BMP PATHWAY

27. TGF- β PATHWAY TGF signaling elicit their cellular response via binding to a tetrameric receptor complex comprising two TGF- β 1(T β R1) and two type II kinase receptors (T β R II). SMAD are the proteins that are the main signal transducer for receptor of Transforming Growth Factor (TGF- β ).

28. FGF PATHWAY

29. PDGF PATHWAY The Platelet derived growth factor has two receptors – α type and β type. The alpha type binds to PDGF-AA, PDGF-BB and PDGF-AB, whereas the beta type PDGFR binds with high affinity to PDGF-BB and PDGF-AB.

30. IGF PATHWAY

31. PARATHYROID HORMONE PARATHYROID HORMONE ANABOLIC EFFECT CATABOLIC EFFECT STIMULATE BONE FORMATION THROUGH TGF- β & IGF-1 STIMULATE BONE RESORPTION INDIRECTLY

32. VITAMIN D3 VITAMIN D3 ANABOLIC EFFECT CATABOLIC EFFECT primary function in Ca absorption from intestine Stimulate bone resorption Supresses Collagen production

33. GLUCOCORTICOIDS GLUCOCORTICOIDS ANABOLIC EFFECT CATABOLIC EFFECT Promotes differentiation of osteoblastic cells Stimulates bone matrix formation

34. THYROID HORMONE THYROID HORMONE – ANABOLIC EFFECT – affects the endochondral bone formation by its action on cartilage formation.

35. OSTEOBLAST Osteoblast are the cells with a single nucleus that synthesizes bone. Osteoblasts are specialized, terminally differentiated products of mesenchymal stem cells. They synthesize dense, crosslinked  collagen and specialized proteins in much smaller quantities, including  osteocalcin, o steonectin , osteopontin , which compose the organic matrix of bone . As Osteocalcin { bone gamma- carboxyglutamic acid-containing protein  ( BGLAP )} is produced by osteoblasts, it is often used as a marker for the bone formation process. Osteopontin (OPN) , also known as bone sialoprotein I (BSP-1 or BNSP ), secreted phosphoprotein 1 (SPP1),  is a  protein that in humans is encoded by the  SPP1   gene. Osteonectin  (ON) also known as  secreted protein acidic and rich in cysteine  (SPARC) is a protein that in humans is encoded by the  SPARC   gene. Before the organic matrix is mineralized, it is called the osteoid. 

36. OSTEOCYTE Osteocytes are the cells that generally helps in bone remodeling and detect micro damage in bone. When osteoblasts become trapped in the matrix that they secrete, they become osteocytes. Osteocytes are networked to each other via long cytoplasmic extensions that occupy tiny canals called canaliculi, which are used for exchange of nutrients and waste through  gap junctions. It also helps to maintain the protein and mineral content of the matrix.

37. OSTEOCLAST Osteoclasts are the cells that helps in bone resorption or the cells that break down the bone tissue.   Osteoclasts are found in pits in the bone surface which are called resorption bays, or  Howship's Lacunae.

38. FORMATION OF BONE Mainly there are two types of ossification : 1. Intramembranous ossification 2. Endochondral ossification

39. ENDOCHONDRAL OSSIFICATION

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