Lec Bone tissue .pdf

BoNE ↳ special type of connective tissue Tisroblasts located > - fibrous layer in = periosteare i > I ASTEDBLAST " - ASTECyte ca > - in allagen recete matrix = - when bone matrix mineralised BONE MATRIX - - organic portion inorganic - collagen type = in = ! collage...

BoNE ↳ special type of connective tissue Tisroblasts located > - fibrous layer in = periosteare i > I ASTEDBLAST " - ASTECyte ca > - in allagen recete matrix = - when bone matrix mineralised BONE MATRIX - - organic portion inorganic - collagen type = in = ! collagen type to which form scaffold Cat and phosphate bind = - - - · · · - a Bone Issue Bant-unmineralised part-ca and Phosphate port-collagen home lating cells a remodelling YEARS giant in BONE-mineralised Immature OSTED CALCIN Osterclass ↳ MATURE : OstEDPONTIN unmineralised 5 through OSTEDNECTIN mineralised EVERY PROCESS MINERALIZATION mononucleated all from diffusion of monocytes Vascular/need for Calcium and Phosphate for Cone mineralization 12/13/20 Bone Carlos E. de Andrea, MD, PhD Department of Histology [email protected] Peer Group Learning: our clinical case… Clinical Presentation Young adult, athlete, presenting initially with pain that is present only during the inciting activity. If the activity level is not decreased or modified, symptoms usually persist or worsen. The patient cannot recall a specific injury or trauma to the injury site. Fractures in Athletes. Springer, Cham. https://doi.org/10.1007/978-3-319-09238-6_14 1 12/13/20 Peer Group Learning: our clinical case… CT scan demonstrates fracture callus present Fractures in Athletes. Springer, Cham. https://doi.org/10.1007/978-3-319-09238-6_14 Peer Group Learning: our clinical case… Questions for you: normal vs abnormal Types of tissues and describe the biological processes… https://www.virtualpathology.leeds.ac.uk/slides/library/view.php?path=%2FResear ch_4%2FTeaching%2FEducation%2FUndergraduate%2F1086.svs 2 12/13/20 Bone - Specialized type of connective tissue with a calcified extracellular matrix in which characteristic cells are embedded - Functions: 1) to support and protect vital organs, and fleshy structures – hematopoietic organs 2) provides a storage site for phosphate and calcium (bone contains about 99% of the body's calcium) Type of Bones http://anatomyandphysiologyi.com/wpcontent/uploads/2014/07/Classification-ofbones.gif 3 12/13/20 Compact (dense) and Spongy (cancellous) Bone Long Bones http://anatomyandphysiologyi.com/wpcontent/uploads/2014/07/Classification-ofbones.gif 4 12/13/20 Bone - Structure 1. Bone Matrix - The inorganic (calcified) portion: calcium, phosphate, bicarbonate, citrate hydroxyapatite crystals - The organic portion: type I collagen (95%) and type V collagen, ground substance that contains chondroitin sulfate, keratan sulfate, and hyaluronic acid Cartilage Water content: ~70% Collagen II: ~40% of organic content. Bone Water content: 25% Collagen I: 90% of organic content. Other Ground Substance Osteonectin: anchor collagen to bone mineral. Osteocalcin: Calcium binding protein involved in bone calcification. Osteopontin: Binding of osteoblasts and osteoclasts to bone. Grows interstitially and by apposition. Avascular Grows only by apposition. Highly vascular 5 12/13/20 Bone - Structure 2. Periosteum: layer of noncalcified connective tissue covering bone on its external surfaces, except at synovial articulations and muscle attachments - An outer dense fibrous collagenous layer and an inner cellular osteoprogenitor (osteogenic) layer - Sharpey fibers (type I collagen) attach the periosteum to the bone surface - To distribute blood vessels to bone Bone - Structure 3. Endosteum: thin specialized connective tissue that lines the marrow cavities supplies osteoprogenitor cells and osteoblasts for bone growth and repair 6 12/13/20 Bone - Cells 1. Osteocyte - the bone cell 2. Osteoprogenitor cells - cells derived from mesenchymal stem cells - will originate osteoblasts 3. Osteoblasts - secrete bone matrix. Once surrounded with bone matrix - called osteocytes Bone - Cells 4. Bone-lining cells - on the bone surface when there is no active growth, derived from osteoblasts that did not originate osteocytes 5. Osteoclasts - bone-resorbing cells present where bone is being removed or remodeled (reorganized) or where bone has been damaged 7 12/13/20 Mature Bone - Organization 8 12/13/20 Mature Bone – Organization Take Home Message - Periosteum is a dense fibrous connective tissue - Outer fibrous layer – fibrous tissue - Inner (cellular) layer – more cellular and contains the osteoprogenitor cells Mature Bone – Organization Take Home Message - Sharpey’s fibers – Collagen fibers of the periosteum - In ligaments and tendons, these fibers extend directly into the bone tissue, where they are continuous with the collagen fibers of the extracellular matrix of the bone tissue 9 12/13/20 Mature Bone – Organization Take Home Message - Bone is vascularized by blood vessels that penetrate the matrix from the periosteum – perforating (Volkmann’s canals) and central (Haversian canal) Mature Bone – Organization Take Home Message - Endosteum - tissue of both the compact bone facing the marrow cavity and the trabeculae of spongy bone - It is often only one cell layer (endosteal cells) of osteoprogenitor cells that can differentiate into osteoblasts 10 12/13/20 Mature Bone – Organization Take Home Message - Mature bone is largely composed of cylindrical – osteons or Haversian systems Mature Bone – Organization Take Home Message - Osteons are concentric lamellae of bone matrix surrounding a central canal, the osteonal (Haversian) canal, which contains the vascular and nerve supply of the osteon 11 12/13/20 Mature Bone – Organization Take Home Message - Long axis of an osteon is usually parallel to the long axis of the bone - Collagen fibers are laid down parallel to one another in any given lamella but in different directions in adjacent lamellae Mature Bone – Organization Take Home Message - Osteocyte, a bone cell, is located in spaces within bone matrix called lacunae (sing.,lacuna) 12 12/13/20 Mature Bone – Organization Take Home Message - Osteocyte extends numerous processes into small tunnels called canaliculi 13 12/13/20 Back to our clinical case… Immature and Mature Bone Tissue 14 12/13/20 Immature and Mature Bone Tissue Immature Bone - Do not display an organized lamellated appearance: Nonlamellar (interlacing) arrangement of collagen fibers - Woven bone/osteoid: unmineralized, organic portion of the bone matrix that forms prior to the maturation - More cells than the mature bone, randomly arranged 15 12/13/20 Peer Group Learning: Back to our case… Questions for you: identify mature and immature bone… Lamellar vs non-lamellar bone -> What does that mean? https://www.virtualpathology.leeds.ac.uk/slides/library/view.php?path=%2FResear ch_4%2FTeaching%2FEducation%2FUndergraduate%2F1086.svs Mature Bone Haversian system (osteon) /Harversian canal 16 12/13/20 Mature Bone - Formed of cylindrical units called Osteons or Haversian systems - Osteons consist of concentric lamellae of bone matrix surrounding a central canal, the osteonal (Haversian) canal (vascular and nerve supply) - Also called lamellar bone Bone Compact and Cancellous Bone 17 12/13/20 Sponge (cancellous) Bone Title (36 points) 18 12/13/20 Bone Bone synthesize new matrix and participate in matrix degradation (maintaining calcium homeostasis) Maintenance and nutritional support of osteocytes. Regulate the movement of calcium and phosphate into and out of the bone type I collagen and bone matrix proteins (BMPs): initial unmineralized bone (osteoid) Found at sites where bone is being removed Derived from the fusion of mononuclear hemopoietic progenitor cells 19 12/13/20 Bone Microenvironment Comprised of a mineralized extracellular matrix and specific cell types that are under the control of local and systemic factors -1 -1 -2 -2 -1 -2 Nat Rev Cancer. 2011 Jun;11(6):411-25. Bone Microenvironment Video 4 20 12/13/20 Role of Osteoblasts and Osteoclasts in Bone Remodelling Bone mass is maintained by a balance between the activity of osteoblasts (right), which form bone, and osteoclasts (left), which break it down Nat Rev Cancer. 2005 Jan;5(1):21-8 Osteoclasts - Polarized, multinucleated myeloid lineage cells that adhere to the bone surface through αvβ3 integrin form an actin ring, and secrete acid, collagenases and proteases that demineralize the bone matrix and degrade matricellular proteins such as type I collagen - Macrophage colony stimulating factor (M-CSF) and RANKL are important growth factors that support osteoclastogenesis, and they are primarily produced by osteoblasts Nat Rev Cancer. 2011 Jun;11(6):411-25. 21 12/13/20 Osteoclasts RANKL binds to its cognate receptor, RANK, on osteoclast precursors, to induce osteoclastogenesis through the nuclear factorκB (NF-κB), NFATc1 and JUN N-terminal kinase signalling pathways Osteoprotegerin (OPG; also known as TNFRSF11B) is an endogenous decoy receptor of RANKL that inhibits osteoclastogenesis Nat Rev Cancer. 2011 Jun;11(6):411-25. Osteoblasts Mesenchymal stem cells (MSCs) in the bone marrow are directed along the osteoblast lineage through local factors, such as transforming growth factor-β (TGFβ), bone morphogenetic proteins (BMPs) and WNT proteins These pathways lead to the expression of three key transcriptional regulators of osteoblast function: RUNX2, osterix and activating transcription factors (ATFs) Nat Rev Cancer. 2011 Jun;11(6):411-25. 22 12/13/20 The Osteoblast Differentiation Program Osteoclast (EM) Note the ruffled border of the cell and resorbing bone matrix 23 12/13/20 Bone Remodeling Process Bone Remodeling Process 1. It starts with activation of the lining cells, which increase surface expression of RANKL 2. RANKL interacts with its receptor RANK, thus triggering osteoclast differentiation (Activation phase) 3. Osteoclasts resorb bone (Resorption phase), thus allowing the release of factors usually stored in the bone matrix (BMPs, TGFβ, FGFs) that recruit osteoblasts in the resorbed area 4. Once recruited, osteoblasts produce the new bone matrix and promote its mineralization (Formation phase), thus completing the bone remodeling process 24 12/13/20 Back to our clinical case… https://www.virtualpathology.leeds.ac.uk/slides/library/view.php?path=%2FResear ch_4%2FTeaching%2FEducation%2FUndergraduate%2F1086.svs Questions for you: Differential diagnoses… Workup… Conclusions… Bone peer-group discussion Our bones are full of cracks, which form and grow as a result of daily loading activities. Bone is the major structural material in our bodies. Although weaker than many engineering materials, it has one trick that keeps it ahead — Which trick is this? Nature Materials 6, 263 - 268 (2007) 25 12/13/20 Bone peer-group discussion Bone can repair itself Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. Nature Materials 6, 263 - 268 (2007) 26