L15 Skeletal System II - Bone Growth & Repair PDF 2024

IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] L15: Skeletal System II – Bone Growth & Repair RESOURCES: Junqueira’s Basic Histology, 16th Ed. by...

IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] L15: Skeletal System II – Bone Growth & Repair RESOURCES: Junqueira’s Basic Histology, 16th Ed. by Mescher: Ch. 8 Moore’s Essential Clinical Anatomy, 7th Ed. by Agur & Dalley: Ch. 1, pg. 9-17 Principles of Anatomy & Physiology, 16th Ed. By Tortora & Derrickson: Ch. 4 pg. 137, Ch. 6 pg. 181-196 Virtual Slides; Histology Guide OBJECTIVES: At the end of this class, students should be able to: Summarize the types of cells and components in the matrix of bone tissue Describe the composition and function of connective tissue layers that surround bone Differentiate the composition of different types of bone Describe the different ways bones are formed Describe the types of bone growth Explain the process and cells involved in bone remodeling Describe the hormones used in blood calcium homeostasis Explain the stages of bone repair Identify images and digital histological slides of bone tissue I. BONE HISTOLOGY a. Bone tissue features specialized bone cells, bone matrix, and organization; it may be prepared as decalcified tissue or sliced with a saw into thin ground sections b. Specialized cells i. Osteoprogenitor cells 1. Unspecialized stem cells of bone tissue that give rise to osteoblasts 2. Located in the periosteum and endosteum 3. Derived from mesenchymal tissue ii. Osteoblasts 1. Immature bone cells that “Build” bone in a process called bone deposition 2. Found on the surface of bones 3. Typically appear as groups of cuboidal-shaped cells 4. Derived from osteoprogenitor stem cells 5. Osteoid – secretion of collagen from osteoblasts that bind calcium phosphate and calcium hydroxide to form hydroxyapatite in mineralized bone iii. Osteocytes 1. Mature osteoblasts that have been surrounded by bone matrix and reside inside lacunae 2. Living cells that detect mechanical stress and maintain bone matrix 3. Typically appear as small cells surrounded by compact bone 4. Receive nutrients, expend waste, and communicate with other osteocytes via tiny channels called canaliculi iv. Osteoclasts 1. Large, multi-nucleated bone cells that “Carve” away bone in a process known as bone resorption 1 IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] 2. Derived from monocytes, a type of leukocyte (white blood cell) 3. Found on the surface of bones 4. Typically appear as massive, multinucleated cells with: 5. Resorption (Howship) lacunae – cavities in the bone matrix surrounding the osteoclasts 6. Sealing zone – tightly binds the osteoclast to the bone 7. Ruffled border – cell membrane projections into the sealed zone that release low pH fluids, collagenases (-ase = enzyme), and proteases to breakdown organic and inorganic materials c. Bone matrix i. Organic materials (~1/3 of bone) 1. Provides some flexibility to bones and a framework for the inorganic mineral salts & crystals 2. Osteoblast secretions are mainly made of organic material (collagen I, proteoglycan, etc.) called osteoid, which then undergoes calcification 3. Collagen (I) is the most abundant organic substance in bone 4. Osteocalcin functions with other glycoproteins to deposit calcium ions into the matrix 5. Osteonectin – binds calcium ions to collagen 6. Others – proteoglycan aggregates, GAGs, etc. ii. Inorganic materials (~2/3 of bone) 1. Makes bones strong but rigid 2. Calcium hydroxyapatite a. Most abundant inorganic substance in bone b. Creates crystals from combined mineral salts, especially from calcium phosphate and calcium hydroxide 3. Others – potassium, magnesium, sodium, citrate, bicarbonate, etc. d. Coverings of bone i. Periosteum 1. Dense irregular connective tissue covering bone 2. Outer fibrous layer a. Collagen (I) i. Perforating (Sharpey) fibers penetrate the bone matrix and anchor the periosteum to the bone b. Blood vessels and nerves c. Fibroblasts 3. Inner osteogenic layer a. Osteoprogenitor cells ii. Endosteum 1. Thin layer of connective tissue lining the medullary cavity and trabeculae 2. Contain some osteoblasts, osteoprogenitor cells, and few collagen fibers II. TYPES OF BONE TISSUE a. Woven bone i. Immature, newly calcified bone ii. Found in bones undergoing development, growth, or repair b. Compact (cortical) bone tissue 2 IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] i. The strongest type of bone tissue that lies closest to the periosteum and contains very little space ii. It provides support and protection iii. Composed of osteons (Haversian systems), which are units of bone lamellae that surround a central canal filled with blood vessels and nerves iv. Central (osteonic/Haversian) canals contain blood vessels and nerves v. Lacunae – small, hollow cavities containing osteocytes vi. Canaliculi (sing. canaliculus, = little canals) 1. Small passageways that connect lacunae to other lacunae and central canals 2. Allows distribution of nutrients and waste and for communication between osteocytes vii. Lamellae (sing. lamella, = thin plate) – thin plates of compact bone that resemble rings; types include: 1. Concentric – rings of lamellae that surround a single central canal and form an osteon 2. External circumferential – thin plates of compact bone that are arranged around the entire outer circumference of bone, just deep to the periosteum 3. Internal circumferential – thin plates of compact bone that are arranged around the entire inner circumference of bone and line the medullar cavity 4. Interstitial a. Plates that fill the areas between osteons b. Remnants of older osteons from bone remodeling c. Spongy (cancellous) tissue i. Found deep to compact bone ii. Consists of bone trabeculae (= little beams, sing. trabecula) and bone marrow between the trabeculae 1. Lines the medullary cavity and is covered by the endosteum 2. Spaces between each trabecula contain bone marrow iii. Also has lamellae, osteocytes, lacunae, and canaliculi iv. Does not have osteons III. BONE FORMATION a. Initial bone formation in an embryo and fetus, in which connective tissue becomes ossified into bone b. Intramembranous ossification (intra-= within, membranous= membrane) i. Uses mesenchyme to make the flat bones of the skull, most facial bones, the mandible, and the medial part of the clavicle ii. Ossification center develops 1. Mesenchymal cells cluster together and differentiate into osteoprogenitor cells. 2. This cluster of osteoprogenitor cells produces osteoblasts, which begin bone deposition (woven bone) iii. Calcification of matrix 1. Many osteoblasts become surrounded by bone matrix and now reside in lacunae 2. Inorganic material begins to calcify in the bone matrix iv. Trabeculae are formed, and spongy bone and red bone marrow develop v. Remaining mesenchyme condenses around the periphery of the bone to form the periosteum 3 IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] c. Endochondral ossification (endo-= within) i. Uses a cartilage model to create the rest of the bones in the body ii. A hyaline cartilage model is formed 1. Chondroblasts secrete the cartilage matrix, and a perichondrium forms 2. The model provides a general shape of the future bone iii. The cartilage model grows 1. Chondroblasts mature into chondrocytes 2. Interstitial and appositional growth of cartilage occurs 3. Chondrocytes in the center of the bone hypertrophy and then are calcified iv. Primary ossification center forms 1. The first ossification center forms in the center (diaphysis) of the bone 2. The nutrient artery begins supplying this region, which activates osteoblasts 3. The perichondrium is turned into a periosteum 4. Calcification spreads from the diaphysis towards the epiphyses v. Medullary cavity forms from osteoclasts carving away the center of the calcified region vi. Secondary ossification centers develop; epiphyseal arteries activate additional ossification centers in the epiphyses vii. An epiphyseal plate is formed, and articular cartilage covers epiphyses IV. BONE GROWTH a. Lengthwise growth i. Occurs at the epiphyseal plate, where hyaline cartilage continues to grow as it is being calcified ii. In order, the areas of the epiphyseal plate can be identified as: 1. Zone of resting (reserve) cartilage (closest to epiphysis) 2. Zone of proliferating cartilage 3. Zone of hypertrophic cartilage 4. Zone of calcified cartilage 5. Zone of ossification (closest to diaphysis) iii. During puberty, sex hormones increase the rate of calcification iv. Osteoblasts catch up to cartilage and close the epiphyseal plate, which becomes the epiphyseal line b. Growth in thickness (appositional) i. Periosteal osteoprogenitor cells create osteoblasts, which begin bone deposition and begin to surround periosteal blood vessels ii. Periosteum becomes endosteum for these new passageways that become surrounded by new concentric lamellae, creating a new osteon iii. New circumferential lamellae are made as the bone grows in thickness V. BONE REMODELING a. Bone is constantly undergoing replacement of old bone tissue (resorption by osteoclasts) with new bone tissue (deposition by osteoblasts) b. This process allows the bone to be adaptable and plastic, able to change its structure under different types of stress c. Changes in diet, exercise, and lifestyle will affect how bone is remodeled i. Example 1: Someone who does weight training each week will exert heavier strain on certain bones, causing their bones to grow thicker and stronger through bone remodeling 4  IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] ii. Example 2: Allows orthodontists to use constant pressure to move teeth within the mandible or maxilla bones as the bones are being remodeled VI. CALCIUM HOMEOSTASIS a. Blood calcium levels are controlled by hormones affecting calcium resorption from bone, calcium deposition into bone, and calcium absorption in the gastrointestinal tract b. Calcitonin (CT) i. Decreases blood calcium levels ii. Inhibits osteoclastic bone resorption and accelerates calcium deposition into bones c. Parathyroid hormone (PTH) i. Increases blood calcium levels ii. Indirectly stimulates osteoclastic bone resorption iii. Also stimulates the formation of calcitriol d. Calcitriol i. Increases blood calcium levels ii. Promotes absorption of calcium from the gastrointestinal tract VII. BONE REPAIR a. The typical repair of bone fractures involves 3 stages b. Reactive (inflammatory) phase i. Early inflammatory phase involving blood from torn vessels to create a fracture hematoma (= blood tumor, clot) ii. Nearby bone cells die, and cellular debris increases iii. Macrophages, neutrophils, and osteoclasts phagocytize dead and damaged tissue iv. This phase may last for several weeks c. Reparative phase – formation of fibrous cartilage callus i. Fibroblasts from the periosteum migrate to the injury and produce collagen fibers ii. Mesenchymal cells differentiate into chondroblasts and produce fibrous cartilage iii. A fibrocartilage callus is formed and connects the broken bone iv. This phase takes around 3 weeks d. Reparative phase – formation of bony callus i. Osteoprogenitor cells near the fracture produce osteoblasts, which produce spongy bone trabeculae ii. The spongy bone trabeculae replace the fibrous cartilage callus with a bony (hard) callus iii. Bony callus lasts around 3 to 4 months e. Bone remodeling phase i. Osteoclasts resorb any remaining fragments of broken bone and begin reshaping the bony callus ii. Osteoblasts replace the spongy bone of the callus with compact bone iii. After a few months, the bone should be fully healed with a slightly thickened area on the surface of the bone; Unless: iv. Malunion – the bone heals but in an abnormal position v. Nonunion – the bone fails to heal, possibly due to: 1. Ischemia – not enough blood supply to the fracture 2. Interference from other tissues 3. Excessive mobility in the region, creating a pseudoarthrosis (= fake joint) 4. Infection 5 IBSSD 1513/1525 – L15 Matthew Fardoux, M.S. 2024 [email protected] Examples of Study Questions How can you describe the composition of bone tissue? What are the cells in bone tissue? What are their functions? What are the inorganic and organic materials of bone tissue? Can you identify the components of bone tissue in light microscopy? What coverings are found on bones, and what are these coverings made of? What are the three types of bone tissue? What makes them unique? What are osteons, and which type of tissue do they compose? How can you describe the different kinds of lamella? What are trabeculae, and where are they found? What are the two different types of bone formation? How can you describe the processes of bone formation? What type of bones are formed in each of these processes? How can you describe the two types of bone growth? What are the different regions seen during lengthwise growth of bone? How can you identify these regions in light microscopy? What is bone remodeling, and how can you describe the process? What type of hormones help keep blood calcium levels steady? How can you describe each of the stages of bone repair? How can you describe the issues that may arise during bone repair? Sample Exam Questions 1. Osteoclasts are derived from what kind of cells? a. Fibroblasts b. Monocytes c. Osteoprogenitor cells d. Osteocytes 2. Which lamella directly surrounds and forms an osteon? a. Concentric lamella b. External circumferential lamella c. Internal circumferential lamella d. Interstitial lamella 3. Which of these events occurs during the reactive (inflammatory) phase of bone repair? a. A fracture hematoma is formed. b. Chondroblasts produce a fibrocartilage callus. c. Osteoblasts produce new spongy bone trabeculae. d. Osteoclasts begin to reshape the bone. 3. A 2. A 1. B 6