Car$lage and Bone. Kris$ne Kra0s, M.D.

Car$lage and Bone Kris$ne Kra0s, M.D.

Car$lage and Bone Lecture Objec$ves Describe the general func$ons of car$lage and bone. Compare the func$on and composi$on of the three types of car$lage. Describe the two methods of car$lage forma$on. Describe the cells and extracellular matrix of bone. Compare and contrast immature and mature bone. Describe the two methods of bone forma$on.

Car$lage and Bone Lecture Outline Car$lage Func$on and characteris$cs of car$lage Composi$on of car$lage Three types of car$lage Forma$on of car$lage Bone Func$on and characteris$cs of bone Composi$on of bone Two (okay, four) types of bone Forma$on of bone

Car$lage and Bone Lecture Outline Car$lage Func$on and characteris$cs of car$lage

Func$ons and Characteris$cs of Car$lage Car$lage is strong and sort of rigid but also flexible. It can withstand force but it can also bend. It s made of cells (chondroblasts and chondrocytes) and extracellular matrix. Forms the suppor$ng framework of some organs. Lines the surface of ar$cula$ng bones. Forms the template for growth and development of long bones.

Metabolic facts that will make you feel sorry for car$lage Bone is very metabolically ac$ve. Car$lage is not. Bone has a good blood supply. Car$lage does not. Bone usually heals well. Car$lage does not.

Car$lage and Bone Lecture Outline Car$lage Func$on and characteris$cs of car$lage Composi$on of car$lage

Car$lage is a specialized, suppor$ng connec$ve $ssue composed of cells and extracellular matrix. Car$lage Cells Chondroblasts Precursor cells that differen$ate into chondrocytes. Chondrocytes Mature car$lage cells that lie in linle ar$factual lacunae.

Car$lage Extracellular Matrix (ECM) Car$lage ECM is composed of: Collagen and/or elas$c fibers Lots of GAGs and proteoglycans Nice choices! These substances make the ECM firm and resistant to mechanical forces.

Composi$on of ECM in Car$lage

Perichondrium Perichondrium covers the surface of hyaline and elas$c car$lage (but not fibrocar$lage). Dense connec$ve $ssue composed of fibroblasts and type I collagen fibers. Contains blood vessels.

Car$lage is avascular. So what? Car$lage itself has no blood vessels or nerves in its extracellular matrix (bone is a different story). Nutrients must diffuse from perichrondrium through extracellular matrix to chondrocytes. This means metabolic ac$vity is low, the width of car$lage is limited, and car$lage heals poorly.

Car$lage and Bone Lecture Outline Car$lage Func$on and characteris$cs of car$lage Composi$on of car$lage Three types of car$lage

The fibers of the extracellular matrix determine the type of car$lage. Hyaline car$lage Elas$c car$lage Fibrocar$lage Type II collagen fibers Type II collagen fibers and elas$c fibers Type I collagen fibers

Three Types of Car$lage Hyaline car$lage Most common. Ar$cular surfaces of joints, large respiratory passages (nose, larynx, trachea, bronchi), ribsternum junc$on, and epiphyseal plate. Func$ons: support so0 $ssue, line joints, growth of long bones.

Hyaline Car$lage: Histologic Features Perichondrium Chondroblasts Extracellular matrix Chondrocytes

Hyaline ar$cular car$lage

Three Types of Car$lage Hyaline car$lage Elas$c car$lage Located in areas that are pliable and flexible Pinna of ear, external auditory canal, auditory (eustachian) tube, epiglo\s, larynx

Elas$c car$lage: perichondrium

Elas$c car$lage: chondrocytes and matrix

Three Types of Car$lage Hyaline car$lage Elas$c car$lage Fibrocar$lage Located in areas subjected to pulling forces Intervertebral discs, pubic symphysis, and anachments of tendons and ligaments

Fibrocar$lage: collagen fibers

Fibrocar$lage: chondrocytes

Fibrocar$lage: matrix

Car$lage and Bone Lecture Outline Car$lage Func$on and characteris$cs of car$lage Composi$on of car$lage Three types of car$lage Forma$on of car$lage

Two Methods of Car$lage Forma$on Inters$$al growth: growth from within car$lage. Chondrocytes divide and secrete matrix. Apposi$onal growth: growth along the outside of car$lage. Chondroblasts secrete matrix and differen$ate into chondrocytes.

Car$lage and Bone Lecture Outline Car$lage Func$on and characteris$cs of car$lage Composi$on of car$lage Three types of car$lage Forma$on of car$lage Bone Func$on and characteris$cs of bone

Func$ons of Bone Support and protec$on of so0 $ssues ANachment of muscles for movement Loca$on of hematopoie$c bone marrow where blood cells are produced Stores and releases calcium, phosphate and other ions

Characteris$cs of Bone Bone is highly vascularized and very metabolically ac$ve. Bone remodels (turns over) constantly throughout life. Ideally, bone removal occurs at same rate as bone produc$on. Inhibi$on of bone turnover leads to poor quality, unhealthy bone.

Composi$on of Bone Cells Osteoblasts: produce bone matrix Osteocytes: lie in lacunae Osteoclasts: resorb bone Extracellular matrix Organic matrix: osteoid, composed of type I collagen fibers and ground substance Inorganic (mineralized) matrix: hydroxyapa$te

Osteoblasts Found along edge of bone, with osteoid underneath. Ac$ve osteoblasts are cuboidal-columnar with abundant RER, Golgi and secretory granules; inac$ve osteoblasts are flanened.

Make bone! Osteoblast Func$ons Produce osteoid (organic bone matrix) with type I collagen fibers, proteoglycans and glycoproteins. Deposit inorganic hydroxyapa$te crystals: Ca 10 (PO 4 ) 6 (OH) 2 Bone forma$on promoted by testosterone, estrogen, growth hormone, weight-bearing exercise and muscle use.

Osteocytes are involved in maintenance of bone matrix. Their death results in resorp$on of matrix. Each osteocyte sits in its own lacuna. Osteocytes have small, dark, flanened nuclei with minimal rough ER and Golgi. Osteocytes

Mul$nucleated giant cells (20-100 μm). Lie in Howship s lacunae. Arise from fusion of blood monocytes. Numerous lysosomes. Ac$vely resorbing osteoclasts adjacent to bone have cytoplasmic membrane branching ( ruffled border ). Osteoclasts

How do osteoclasts resorb bone? Clear zone: an area of cytoplasm that seals off an acidic micro-environment containing lysosomal enzymes. This is where bone resorp$on occurs.

How do osteoclasts resorb bone? The osteoclast transfers collagenase and protons into this microenvironment, breaking down collagen fibers and calcium salts. Then, the osteoclast phagocy$zes the remnants of bone resorp$on.

Bone Matrix Inorganic 50% of dry weight of bone Mostly calcium Organic Type I collagen Ground substance (proteoglycans and glycoproteins)

Serum Calcium and Bone Resorp$on When serum calcium is low, parathyroid hormone is released, which tells osteoblasts to make osteoclast s$mula$ng factor. Osteoclasts then resorb bone, which increases serum calcium. Cool! When serum calcium is high, calcitonin is released, which inhibits osteoclas$c resorp$on of bone, leading to decreased serum calcium.

Two Gross Types of Bone Compact bone Very dense, solid structure. Spongy bone Open, loose structure.

Compact Bone and Spongy Bone Compact bone Spongy bone

Two Microscopic Types of Bone Immature (primary, woven) bone The first bone laid down. Formed quickly. Later replaced by mature bone. Mature (secondary, lamellar) bone Arranged in osteons: layers (lamellae) of bone around linle canals.

Immature vs. Mature Bone Immature bone Mature bone Gross structure Always spongy Compact (outside) and spongy (inside) Collagen fiber arrangement Random Parallel Number of osteocytes Lots Rela$vely few

Two Microscopic Types of Bone Immature (primary, woven) bone The first bone laid down. Formed quickly. Later replaced by mature bone.

Immature bone: super low-power view

Immature bone: high-power view

Central canal Osteocytes Lamellae Osteon (Haversian system)

Volkmann (perfora$ng) canals connect osteons

Periosteum and Endosteum Periosteum lines the outer surface of compact bone. Two layers: outer dense connec$ve $ssue layer and inner layer of osteoprogenitor cells. Sharpey s fibers are collagen fibers which $ghtly anach the periosteum to the bone matrix. Contains blood vessels for nutri$on of bone. Contains osteoblasts for bone growth, repair and remodeling.

central canal osteon external lamellae Periosteum inner layer outer layer perfora$ng fibers inters$$al lamellae trabeculae of spongy bone

Periosteum and Endosteum Periosteum lines the outer surface of compact bone. Endosteum lines the inner surface of compact bone. Also lines the surface of bony trabeculae of spongy bone, and the Haversian canals. Contains osteoblasts for bone growth, repair and remodeling.

Endosteum

Bone Development (Osteogenesis) Bone can be formed in two ways: Intramembranous ossifica$on Occurs in flat bones (most of skull, including maxilla and mandible). Endochondral ossifica$on Occurs in long bones and irregular bones.

Eight Steps in Intramembranous Ossifica$on 1. Capillaries grow into mesenchyme & release oxygen. 2. Surrounding mesenchymal cells round up, differen$ate into osteoblasts and form osteoid. 3. Osteoid mineralizes. Osteoblasts become osteocytes. 4. Bone spicules form and enlarge to form trabeculae of immature bone. 5. A single plate (table) of bone is formed. 6. Immature bone is replaced by mature bone. 7. Remodeling con$nues, and 2 tables of bone are formed. 8. The two tables are separated by diploe: Tables = compact bone Diploe = spongy bone with marrow

Intramembranous Ossifica$on

Six Steps in Endochondral Ossifica$on 1. Fetal hyaline car$lage develops. 2. Car$lage calcifies, and a periosteal bone collar forms around the diaphysis (long part of the bone). 3. A primary ossifica$on center forms in the diaphysis. 4. Secondary ossifica$on centers form in the epiphyses (ends of the bone). 5. Bone replaces car$lage (except the ar$cular car$lage and epiphyseal plates). 6. Epiphyseal plates ossify.

Endochondral Ossifica$on

Endochondral Ossifica$on Epiphysis: the end of a long bone. Consists primarily of spongy bone, with a layer of compact bone on the outside. Diaphysis: the sha0 of a long bone. Consists of compact bone on the outside and a marrow cavity inside.

Endochondral bone forma$on: super low-power view

Endochondral bone forma$on: zones of matura$on

Endochondral bone forma$on: res$ng zone

Endochondral bone forma$on: prolifera$ve zone

Endochondral bone forma$on: zone of hypertrophy

Endochondral bone forma$on: zone of calcifica$on

Endochondral bone forma$on: zone of ossifica$on

Epiphyseal plate in endochondral ossifica$on

Synovial joint (diarthrosis)

Synovial Membrane

Ar$cular car$lage Joint cavity Synovial membrane