Orthopedics Hyperguide Review | Dr Hutaif General Ortho -...

The three major types of glycosaminoglycans in articular cartilage are chondroitin sulfate, keratan sulfate, and dermatan sulfate. Chondroitin sulfate is the most common glycosaminoglycan in articular cartilage. Chondroitin 4-sulfate and chondroitin 6-sulfate isomers account for 55% to 90% of the total amount.
The glycosaminoglycan chains contain repeating carboxyl and sulfate groups that become ionized in solution. These free-floating ions account for the Donnan osmotiCpressure and the large charge-to-charge repulsive forces of the glycosaminoglycan chains.
Most of the glycosaminoglycans are in the form of large aggregates called aggrecan. Link protein binds to both the G1 domain of aggrecan and the hyaluron chain to form the aggrecan-hyaluronate-link protein complexes, which are called proteoglycan aggregates.

Biglycan and decorin are two small proteoglycans (biglycan has two dermatan sulfate chains and decorin contains one dominant sulfate chain). Decorin is located on the surface of collagen fibrils and is believed to be involved with fibrillogenesis and fibril diameter.

Link protein binds to both the G1 domain of aggrecan and the hyaluronate chain forming the aggregan-hyaluronate-link protein complexes referred to as proteoglycan aggregates.

Articular cartilage receives its nutrition through small pores (approximately 50 angstroms) from the synovial fluid. Adult articular cartilage has no blood supply. Diffusion rates vary between 10 seconds to 1 hour. Degradation products are able to leave the cartilage rapidly.

The proteins for glycosaminoglycan synthesis are synthesized in the ribosomes. The glycosaminoglycan chains are added in the Golgi apparatus. Protoeglycan aggregates are formed in the extracellular matrix where link protein, hyaluronate, and aggrecan come together. Many factors may influence the quantity and makeup of the proteoglycans.
Glycosaminoglycan chains are formed intracellularly, whereas large proteoglycan aggregates are formed outside the cell in the extracellular matrix.

The proteins for glycosaminoglycan synthesis are synthesized in the ribosomes (hence, intracellular). The glycosaminoglycan chains are added in the Golgi apparatus. Protoeglycan aggregates are formed in the extracellular matrix where link protein, hyaluronate, and aggrecan come together. Many factors may influence the quantity and makeup of the proteoglycans.

There are several important points concerning aging and articular cartilage. The collagen content increases quickly after birth, attaining adult levels, and then it does not materially change. The water level is high in immature individuals but remains constant in the adult. In contrast to the stable levels of collagen and water, the proteoglycan composition changes:
Chondroitin 4-sulfate levels progressively decrease. Chondroitin 6-sulfate levels progressively increase.
Keratan sulfate levels progressively increase in the human. At age 30, the level increases to 25% to 50% of proteoglycan content.
Aggregation decreases with advancing age.

Cartilage is a biphasiCmaterial. Water and the solid matrix (collagen and the proteoglycans) account for this behavior. Articular cartilage is viscoelastiCand will exhibit time-dependent behavior. There are two mechanisms for the viscoelasticity. One mechanism is flow independent. The flow independent behavior derives from the collagen-proteoglycan matrix. The flow dependent mechanism depends on the interstitial fluid flow and pressurization.
Cartilage must be compressed for 2.5 to 6 hours before the interstitial fluid flow ends and the load is fully borne by the collagen proteoglycan matrix (this virtually never happens in humans). The ratio of load supported by the fluid pressure to that supported by solid matrix is greater than 20:1.
In osteoarthritis cartilage, there is increased water content and decreased proteoglycan content. These changes increase cartilage permeability and lower the ability to carry load.

Reduced joint motion and loading results in decreased proteoglycan concentration. Collagen concentration does not change. Normal tensile properties are maintained which reflect the relatively constant collagen concentration. Nutrition of the joint decreases because of reduced loading.

Type II, IX, and XI collagen forms a fibrillar network that gives cartilage its form and tensile stiffness and strength. Type VI collagen forms part of the matrix immediately surrounding chondrocytes and may help attach the cells attach to the matrix macromolecular framework.

The genetiCdefect in achondroplasia involves fibroblast growth factor (FGF) receptor 3.
The other answers refer to:
Osteogenesis imperfecta Type I collagen
Marfan syndrome Fibrillin
Spondyloepiphyseal
dysplasia Type II collagen
Pseudoachondroplasia Cartilage oligomeriCmatrix protein (COMP) Correct Answer: Fibroblast growth factor (FGF) receptor 3

Osteogenesis imperfecta has been linked to defect in type I collagen.
The other answers refer to:
Achondroplasia Fibroblast growth factor (FGF) receptor 3
Marfan syndrome Fibrillin
Spondyloepiphyseal
dysplasia Type II collagen
Pseudoachondroplasia Cartilage oligomeriCmatrix protein (COMP) Correct Answer: Type I collagen

The genetiCdefect in pseudoachondroplasia involves cartilage oligomeriCmatrix protein (COMP). The other answers refer to:
Achondroplasia Fibroblast growth factor (FGF) receptor 3
Marfan syndrome Fibrillin
Spondyloepiphyseal
dysplasia Type II collagen
Osteogenesis imperfecta Type I collagen

The molecular defect in Marfan syndrome involves fibrillin. The other answers refer to:
Achondroplasia Fibroblast growth factor (FGF) receptor 3
Pseudoachondroplasia Cartilage oligomeriCmatrix protein (COMP) Spondyloepiphyseal
dysplasia Type II collagen
Osteogenesis imperfecta Type I collagen

The genetiCdefect in spondyloepiphyseal dysplasia involves type II collagen.
The other answers refer to:
Achondroplasia Fibroblast growth factor (FGF) receptor 3
Pseudoachondroplasia Cartilage oligomeriCmatrix protein (COMP) Marfan syndrome Fibrillin
Osteogenesis
imperfecta Type I collagen

In Duchenne muscular dystrophy, the genetiCdefect involves dystrophin. The other answers refer to:
X-linked hypophosphatemic
rickets PEX (a cellular endopeptidase)
Osteopetrosis CarboniCanhydrase type II proton pump
Fibrous dysplasia Gs alpha (receptor-coupled signaling protein)
Multiple hereditary exostoses EXT1, EXT2 genes

The genetiCdefect in X-linked hypophosphatemiCrickets involves PEX (a cellular endopeptidase).
The other answers refer to:
Duchenne muscular dystrophy
Â
Dystrophin
Osteopetrosis CarboniCanhydrase type II proton pump
Fibrous dysplasia Gs alpha (receptor-coupled signaling protein)
Multiple hereditary exostoses EXT1, EXT2 genes

The genetiCdefect in osteopetrosis involves the carboniCanhydrase type II proton pump.
The other answers refer to:
Duchenne muscular dystrophy
 Dystrophin
X-linked hypophosphatemic
rickets PEX (a cellular endopeptidase)
Fibrous dysplasia Gs alpha (receptor-coupled signaling protein)
Multiple hereditary exostoses EXT1, EXT2 genes

The genetiCdefect in fibrous dysplasia involves an activity mutation of Gs alpha (a receptor coupled signaling protein).
The other answers refer to:
Duchenne muscular dystrophy
 Dystrophin
X-linked hypophosphatemic
rickets PEX (a cellular endopeptidase)
Osteopetrosis CarboniCanhydrase type II proton pump
Multiple hereditary exostoses EXT1, EXT2 genes

The genetiCdefect in multiple hereditary exostoses involves EXT1 and EXT2 genes. The other answers refer to:
Duchenne muscular dystrophy Dystrophin
X-linked hypophosphatemic
rickets PEX (a cellular endopeptidase)
Osteopetrosis CarboniCanhydrase type II proton pump
Fibrous dysplasia Gs alpha (receptor-coupled signaling protein) Correct Answer: EXT1, EXT2 genes

Woven bone is immature bone that is found in newborns, fracture callus, and the metaphyses of growing bone. In woven bone, the collagen fibers are oriented in a completely random fashion. When woven bone is loaded, it performs in an isotropiCmanner. The other types of bone (lamellar, cortical, cancellous, and plexiform) contain collagen that is oriented along the long axis of the bone and cause the bone to perform anisotropically.

The osteon is a unique arrangement of bone cells and matrix surrounding a blood vessel. The osteon is an irregular branching, anastomosing cylinder composed of a centrally placed neurovascular canal surrounded by cell-permeated layers of bone matrix.
The bone remodeling unit refers to the cutting cone of leading osteoclasts and following osteoblasts.
Plexiform bone is a structural type of bone found in large animals where rapid bone growth occurs. There are alternating layers of lamellar and woven bone.
Volkman canals are the channels connecting different osteons or Haversian units.
Canaliculi are small channels through which the cell processes of the osteocytes connect to each other. Correct Answer: Osteon

The normal porosity of cortical bone is 10% compared to trabecular bone, which is 50% to 90%. Cortical bone porosity occurs because of the Haversian and Volkman canals and, to a lesser extent, from the osteocyte lacunae and canaliculi.
Trabecular bone is arranged as a series of interconnecting small plates and rods. The porosity may vary between 50% to 90%. This porosity is secondary to the spaces between the trabecular pieces of bone rather than voids in the actual pieces of trabecular bone.

Trabecular bone is arranged as a series of interconnecting small plates and rods. The porosity may vary between 50% to 90%. This porosity is secondary to the spaces between the trabecular pieces of bone rather than voids in the actual pieces of trabecular bone.
The normal porosity of cortical bone is 10%. Cortical bone porosity occurs because of the Haversian and Volkman canals and, to a lesser extent, from the ostocyte lacunae and canaliculi.

Osteoblasts are metabolically active cells that line the bone surface. Osteoblasts produce type I collagen and many
noncollagenous proteins such as osteocalcin, bone sialoprotein, and extracellular matrix proteins. Osteoblasts have large amounts of rough endoplasmiCreticulum because they prepare large amounts of protein for export out of the cell. The Golgi apparatus exports the protein.

Osteoblasts produce type I collagen. This is the major type of collagen found in bone. Type I collagen is the only collagen capable of mineralization.

Osteoblasts that become imbedded into the bone matrix become osteocytes. Osteocytes are less metabolically active because they do not produce large amounts of protein for export. Thus, osteocytes have a higher nucleus to cytoplasm ratio than osteoblasts. Osteocytes have fewer organelles as they do not need extensive intracellular machinery to export protein products.
Osteocytes have extensive connections with other osteocytes through the cell processes that travel through the canaliculi. Strain generated signals such as cell deformation, streaming potentials, or shear stress by fluid flow could be perceived by the osteocytes and passed on to other cells.
Osteocytes do not line the bone surface as osteoblasts do. In addition, osteoblasts have alkaline phosphatase covering the cell membranes.

Active osteoclasts resorb the mineral and organiCmatrix of bone. Active osteoclasts also attach the cell to exposed bone matrix. When osteoclasts are studied with an electron microscope, there are two prominent findings â a ruffled border and a clear zone. In the clear zone, the osteoclast seals off the area of bone to be resorbed and attaches to the bone surface through a receptor- mediated process with the assistance of proteins called integrins. The ruffled border is an area found in the infoldings of the cell membrane. At the area of the ruffled border, the osteoclasts lower the pH with hydrogen ions through the carboniCanhydrase system. This lowered pH increases the solubility of the apatite crystals and the mineral can be removed. The organiCcomponents of the bone are then hydrolyzed through acidiCproteolytiCdigestion.

Active osteoclasts resorb the mineral and organiCmatrix of bone. Active osteoclasts also attach the cell to exposed bone matrix. When osteoclasts are studied with an electron microscope, there are two prominent findings â a ruffled border and a clear zone. In the clear zone, the osteoclast seals off the area of bone to be resorbed and attaches to the bone surface through a receptor- mediated process with the assistance of proteins called integrins. The ruffled border is an area found in the infoldings of the cell membrane. At the area of the ruffled border, the osteoclasts lower the pH with hydrogen ions through the carboniCanhydrase system. This lowered pH increases the solubility of the apatite crystals and the mineral can be removed. The organiCcomponents of the bone are then hydrolyzed through acidiCproteolytiCdigestion.

Osteoblasts have receptors for parathyroid hormone, vitamin D, testosterone, thyroid hormone, and glucocorticoids. Osteoblasts receive the majority of systemiCendocrine-based signals. The osteoblasts, which are in physical contact with the osteocytes through osteocytiCcell processes, transmit the signals to the osteoclasts.
In contrast, strain generated signals, such as cell deformation, streaming potentials, or shear stress caused by fluid flow, are received by the osteocyte and transmitted to other cells.

Osteoblasts can be active metabolically or in a resting phase. Active osteoblasts are plump in shape with a low nucleus to cytoplasm ratio and they produce and excrete both type I collagen and noncollagenous proteins that make up the bone matrix.
In contrast, resting bone-lining cells are not metabolically active compared to the active osteoblasts. The resting bone-lining cells are elongated and flat. These cells secrete enzyme-regulating proteins such as collagenase, collagenase inhibitor, and plasminogen activator. These enzymes help to control bone degradation. The osteoblasts respond to parathyroid hormone, 1,25 dihydroxyvitamin D3, and prostaglandins of the E series. The osteoblasts withdraw from the bone surface, begin degradation with their enzymes, and then the osteoclasts move in and resorb the inorganiCand organiCmatrix of bone.

Osteoblasts have receptors for parathyroid hormone, prostaglandins, 1,25 dihydroxyvitamin D3, glucocorticoids, and estrogen. Although the osteoblasts have receptors for estrogen, their exact role is unknown.

The resting bone-lining cells (flat, elongated osteoblasts) begin the bone resorption process by secreting collagenases that degrade the osteoid layer covering bone. These cells may also contract to expose the bone surface and allow access for the osteoclasts.
Parathyroid hormone (PTH) mediates bone resorption by stimulation of PTH receptors on the osteoblasts. Osteoclasts do not have receptors for PTH.

Active osteoclasts resorb the mineral and organiCmatrix of bone and attach to the exposed bone matrix. When osteoclasts are studied with an electron microscope, there are two prominent findings â a ruffled border and a clear zone. In the clear zone, the osteoclast seals off the area of bone to be resorbed by attaching to the bone surface. The osteoclast attaches to the bone surface through a receptor-mediated process with the assistance of proteins called integrins. The ruffled border is an area found in the infoldings of the cell membrane. At the area of the ruffled border, the osteoclasts lower the pH with hydrogen ions through the carboniCanhydrase system. This lowered pH increases the solubility of the apatite crystals and the mineral can be removed. The organiCcomponents of the bone are then hydrolyzed through acidiCproteolytiCdigestion.

Parathyroid hormone (PTH) mediates bone resorption by stimulation of PTH receptors on the osteoblasts. Osteoclasts do not have receptors for PTH.

Bone has the following composition:
Mineral or inorganiCphase 70% Water 5% to 8% OrganiCmatrix 22% to 25% Collagen type I 90% Noncollagenous proteins 5% to 8%

Bone has the following composition:
Mineral or inorganiCphase 70% Water 5% to 8% OrganiCmatrix 22% to 25% Collagen type I 90% Noncollagenous proteins 5% to 8%

Bone sialoproteins are important in the initiation of mineralization of collagen. They promote apatite nucleation and growth of the crystals. Osteocalcin (bone Gla protein) is important for mineral proliferation and maturation.
Note the role of promoters and inhibitors: Apatite nucleation and growth Promoters
Type I collagen Bone sialoprotein Matrix vesicles Phosphoproteins Proteolipids Biglycan
Inhibitors
Large proteoglycans Pyrophosphate Adenosine triphosphate Citrate
Mineral proliferation
Regulators
Osteocalcin Phosphoproteins Proteoglycans

Bone sialoproteins are important in the initiation of mineralization of collagen. They promote apatite nucleation and growth of the crystals. Osteocalcin (bone Gla protein) is important for mineral proliferation and maturation.
Note the role of promoters and inhibitors: Apatite nucleation and growth Promoters
Type I collagen Bone sialoprotein Matrix vesicles Phosphoproteins Proteolipids Biglycan
Inhibitors
Large proteoglycans Pyrophosphate Adenosine triphosphate Citrate
Mineral proliferation
Regulators
Osteocalcin Phosphoproteins Proteoglycans

Only type I collagen is capable of supporting mineralization. Correct Answer: Type I

Bone sialoproteins (phosphoproteins) are important in the initiation of mineralization of collagen. They promote apatite nucleation and growth of the crystals. Large proteoglycans, pyrophosphates, adenosine triphosphate, and citrate are all inhibitors.
Note the role of promoters and inhibitors: Apatite nucleation and growth Promoters
Type I collagen Bone sialoprotein Matrix vesicles Phosphoproteins Proteolipids Biglycan
Inhibitors
Large proteoglycans Pyrophosphate Adenosine triphosphate Citrate
Mineral proliferation
Regulators
Osteocalcin Phosphoproteins Proteoglycans

Bone sialoproteins are important in the initiation of mineralization of collagen. They promote apatite nucleation and growth of the crystals. Large proteoglycans, pyrophosphates, adenosine triphosphate, and citrate are all inhibitors.
Note the role of promoters and inhibitors: Apatite nucleation and growth Promoters
Type I collagen Bone sialoprotein Matrix vesicles Phosphoproteins Proteolipids Biglycan
Inhibitors
Large proteoglycans Pyrophosphate Adenosine triphosphate Citrate
Mineral proliferation
Regulators
Osteocalcin Phosphoproteins Proteoglycans

Matrix vesicles are important in the initiation of mineralization of collagen. They promote apatite nucleation and growth of the crystals. Large proteoglycans, pyrophosphates, adenosine triphosphate, and citrate are all inhibitors.
Note the role of promoters and inhibitors: Apatite nucleation and growth Promoters
Type I collagen Bone sialoprotein Matrix vesicles Phosphoproteins Proteolipids Biglycan
Inhibitors
Large proteoglycans Pyrophosphate Adenosine triphosphate Citrate
Mineral proliferation
Regulators
Osteocalcin Phosphoproteins Proteoglycans

Large proteoglycans, pyrophosphate, adenosine triphosphate, and citrate all act as inhibitors of physiologiCcalcification of bone. Note the role of promoters and inhibitors:
Apatite nucleation and growth
Promoters
Type I collagen Bone sialoprotein Matrix vesicles Phosphoproteins Proteolipids Biglycan
Inhibitors
Large proteoglycans Pyrophosphate Adenosine triphosphate Citrate
Mineral proliferation
Regulators
Osteocalcin Phosphoproteins Proteoglycans

Cortical bone remodeling can be as high as 50% in the femoral diaphysis during the first 2 years of life. In older adults, the cortical remodeling rate is only 2% to 5% per year. Trabecular bone remodels at a rate 5 to 10 times higher than cortical bone.

The periosteal vessels supply 15% to 20% of the outer periosteal surface. There are three defined blood supplies:
Nutrient vessel entering in the diaphysis
Metaphyseal vessels from the periarticular vessels (geniculate vessels) Periosteal vessels supply the outer 15% to 20% of the cortex

Dietary calcium is absorbed in the small intestine. This absorption is stimulated by 1,25 dihydroxyvitamin D3. Correct Answer: Small intestine

One hour of sunlight per day is necessary in white people to convert 7-dehydrocholesterol to vitamin D3 (cholecalciferol). A longer exposure is necessary in dark-skinned people.