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Question 3661

Topic: 1. General Principles & Basic Science

In normal hyaline articular cartilage, which of the following collagen types is primarily responsible for covalently cross-linking the Type II collagen fibrils to the surrounding proteoglycan network?

. Type I
. Type VI
. Type IX
. Type X
. Type XI

Correct Answer & Explanation

. Type I


Explanation

Type IX collagen is a Fibril Associated Collagen with Interrupted Triple helices (FACIT) that covalently binds to the surface of Type II collagen fibrils. It plays a critical role in mediating the intersection and cross-linking of the fibril network with the proteoglycan-rich extracellular matrix.

Question 3662

Topic: 1. General Principles & Basic Science

The compressive stiffness of articular cartilage is heavily dependent on the presence of aggrecan molecules. Which of the following glycosaminoglycans represents the most abundant side chain covalently attached to the core protein of aggrecan?

. Keratan sulfate
. Chondroitin sulfate
. Dermatan sulfate
. Hyaluronic acid
. Heparan sulfate

Correct Answer & Explanation

. Keratan sulfate


Explanation

Chondroitin sulfate is the most abundant glycosaminoglycan (GAG) in articular cartilage. It binds to the aggrecan core protein. These aggrecan monomers then non-covalently bind to a long hyaluronic acid backbone via link proteins to form massive proteoglycan aggregates, which confer compressive stiffness by creating a high osmotic swelling pressure.

Question 3663

Topic: 1. General Principles & Basic Science

At the onset of joint movement under high contact loads, which lubrication mechanism is primarily responsible for reducing friction between the opposing articular cartilage surfaces?

. Elastohydrodynamic lubrication
. Squeeze-film lubrication
. Boundary lubrication
. Hydrodynamic lubrication
. Weeping lubrication

Correct Answer & Explanation

. Elastohydrodynamic lubrication


Explanation

Boundary lubrication is the primary mechanism reducing friction under high loads and low speeds, such as at the onset of motion. It is mediated by molecules like lubricin (PRG4) that bind directly to the articular surface. Fluid-film mechanisms (like elastohydrodynamic and squeeze-film) predominate during continuous, higher-speed motion.

Question 3664

Topic: 1. General Principles & Basic Science
In the pathogenesis of early primary osteoarthritis, enzymatic degradation of the articular cartilage extracellular matrix is a hallmark feature. Which of the following enzymes is predominantly responsible for the primary cleavage and degradation of the type II collagen network?
. ADAMTS-4
. MMP-13 (Collagenase-3)
. Tissue Inhibitors of Metalloproteinases (TIMPs)
. Cathepsin K
. MMP-3 (Stromelysin-1)

Correct Answer & Explanation

. MMP-13 (Collagenase-3)


Explanation

Matrix metalloproteinase-13 (MMP-13), also known as collagenase-3, is the principal enzyme responsible for the cleavage and destruction of type II collagen in osteoarthritis. ADAMTS-4 and ADAMTS-5 are aggrecanases that primarily degrade aggrecan (proteoglycans), which usually precedes collagen degradation.

Question 3665

Topic: 1. General Principles & Basic Science

A 35-year-old male with early hip dysplasia is evaluated for a periacetabular osteotomy (PAO). To non-invasively assess the biochemical integrity of the hip articular cartilage, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is ordered. What is the physiological basis of this specific imaging modality?

. Gadolinium selectively binds to intact type II collagen fibers to provide hyperintense signals
. Gadolinium distributes inversely to the glycosaminoglycan (GAG) concentration because both are negatively charged
. Gadolinium accumulates in areas of increased water content due to chondrocyte swelling
. Gadolinium binds directly to the chondroitin sulfate side chains of the aggrecan molecule
. Gadolinium enhances the visualization of subchondral bone edema that precedes cartilage loss

Correct Answer & Explanation

. Gadolinium selectively binds to intact type II collagen fibers to provide hyperintense signals


Explanation

The contrast agent used in dGEMRIC (Gd-DTPA2-) is negatively charged. Glycosaminoglycans (GAGs) in normal healthy cartilage are also highly negatively charged. Due to electrostatic repulsion, the contrast agent distributes inversely proportional to the GAG concentration. High contrast uptake indicates low GAG content, signaling early cartilage degeneration.

Question 3666

Topic: 1. General Principles & Basic Science

Which of the following biochemical profiles most accurately distinguishes articular cartilage undergoing early osteoarthritic (OA) degeneration from articular cartilage undergoing normal physiologic aging?

. OA cartilage has decreased water content; aging cartilage has increased water content.
. OA cartilage has increased total proteoglycan content; aging cartilage has decreased total proteoglycan content.
. OA cartilage has increased water content and decreased total proteoglycans; aging cartilage has decreased water content and decreased total proteoglycans.
. OA cartilage has decreased chondroitin sulfate; aging cartilage has increased keratin sulfate and increased water content.
. OA cartilage has an increased ratio of chondroitin-6-sulfate to chondroitin-4-sulfate; aging cartilage has decreased water and increased proteoglycan size.

Correct Answer & Explanation

. OA cartilage has decreased water content; aging cartilage has increased water content.


Explanation

A hallmark difference between osteoarthritis (OA) and normal aging in articular cartilage is the water content. In early OA, the collagen network is damaged, allowing proteoglycans to swell, resulting in increased water content, accompanied by a decrease in total proteoglycan concentration. In contrast, normal aging cartilage exhibits decreased water content, decreased total proteoglycans, and increased chondroitin-6-sulfate relative to chondroitin-4-sulfate.

Question 3667

Topic: 1. General Principles & Basic Science

Articular cartilage is divided into distinct anatomical zones. Which of the following accurately describes the 'Deep Zone' of normal mature articular cartilage?

. It contains the highest concentration of water and collagen fibers oriented parallel to the joint surface.
. It represents the largest volume of the cartilage and contains randomly oriented collagen fibers.
. It contains the highest concentration of proteoglycans with chondrocytes arranged in columns perpendicular to the joint surface.
. It is located deep to the tidemark and represents the calcified transition to subchondral bone.
. It has the highest cellularity and primarily secretes Type I collagen.

Correct Answer & Explanation

. It contains the highest concentration of proteoglycans with chondrocytes arranged in columns perpendicular to the joint surface.


Explanation

The deep (basal) zone of articular cartilage contains the highest concentration of proteoglycans (and correspondingly the lowest water content). The collagen fibers (Type II) are oriented perpendicular to the articular surface, crossing the tidemark to anchor into the calcified cartilage. The chondrocytes in this zone are distinctly arranged in vertical columns parallel to the collagen fibers. The superficial zone has the highest water content and parallel collagen fibers.

Question 3668

Topic: 1. General Principles & Basic Science

Which zone of articular cartilage has the highest concentration of water and the lowest concentration of proteoglycans?

. Superficial zone
. Transitional (middle) zone
. Deep zone
. Calcified zone
. Tidemark

Correct Answer & Explanation

. Superficial zone


Explanation

The superficial (tangential) zone of articular cartilage has the highest water content (approx. 80%), the lowest proteoglycan content, and densely packed collagen fibrils aligned parallel to the joint surface to resist shear stress.

Question 3669

Topic: 1. General Principles & Basic Science

Boundary lubrication of articular cartilage is primarily mediated by which of the following molecules?

. Hyaluronic acid
. Chondroitin sulfate
. Lubricin (PRG4)
. Aggrecan
. Type II collagen

Correct Answer & Explanation

. Lubricin (PRG4)


Explanation

Boundary lubrication is crucial for reducing friction between apposing cartilage surfaces under high loads and low velocities. It is primarily mediated by lubricin (proteoglycan 4 or PRG4), a glycoprotein synthesized by superficial zone chondrocytes and synoviocytes.

Question 3670

Topic: 1. General Principles & Basic Science

Which of the following components of the articular cartilage extracellular matrix is responsible for creating the Donnan osmotic swelling pressure that imparts compressive stiffness?

. Decorin
. Type IX collagen
. Fixed negative charges on glycosaminoglycan sulfate and carboxyl groups
. Fixed positive charges on the hyaluronic acid backbone
. Covalent cross-links between Type II collagen and aggrecan

Correct Answer & Explanation

. Fixed negative charges on glycosaminoglycan sulfate and carboxyl groups


Explanation

The high density of fixed negative charges on the sulfated glycosaminoglycans (chondroitin and keratin sulfate) repels adjacent charges and attracts cations (like Na+) and water. This creates a strong osmotic gradient (the Donnan effect) that exerts a swelling pressure. The tension of the collagen network constrains this swelling, providing articular cartilage with its compressive stiffness.

Question 3671

Topic: Biology, Genetics & Bone Healing

Which transcription factor is considered the master regulator of chondrogenesis and is essential for the expression of Type II collagen and aggrecan during skeletal development?

. SOX9
. RUNX2
. Osterix
. HIF-1 alpha
. Scleraxis

Correct Answer & Explanation

. SOX9


Explanation

SOX9 is the master regulatory transcription factor for chondrogenesis. It directly binds to and activates enhancer elements of key cartilage matrix genes, including COL2A1 (Type II collagen) and ACAN (aggrecan). RUNX2 and Osterix are key regulators of osteogenesis. Scleraxis is associated with tenogenesis/ligamentogenesis.

Question 3672

Topic: 1. General Principles & Basic Science

Which of the following extracellular matrix changes differentiates early osteoarthritic cartilage from normally aging articular cartilage?

. Increased water content
. Decreased chondrocyte size
. Increased proteoglycan concentration
. Increased ratio of chondroitin sulfate to keratin sulfate
. Decreased advanced glycation end-products (AGEs)

Correct Answer & Explanation

. Increased water content


Explanation

In normally aging cartilage, water content decreases. In early osteoarthritis, however, the collagen network is disrupted and degraded, allowing the constrained proteoglycans to expand and draw in more fluid, leading to an paradoxicalincreasein water content (cartilage swelling). Proteoglycan content generally decreases as OA progresses.

Question 3673

Topic: Physiology & Rehabilitation

During the stance phase of the normal human gait cycle, the joint reaction force across the hip joint typically peaks at approximately what multiple of body weight?

. 1 times body weight
. 2.5 to 3 times body weight
. 5 to 6 times body weight
. 8 to 10 times body weight
. Less than body weight due to the abductor counter-moment

Correct Answer & Explanation

. 1 times body weight


Explanation

During normal walking, the hip joint reaction force peaks at approximately 2.5 to 3 times body weight during the stance phase. This force is the vector sum of body weight acting on a longer lever arm and the substantial counterbalancing pull of the abductor musculature acting on a shorter lever arm.

Question 3674

Topic: 1. General Principles & Basic Science
In the early pathogenesis of osteoarthritis, the initial degradation and depletion of the aggrecan molecule from the extracellular matrix is primarily mediated by which of the following enzyme families?
. Matrix metalloproteinase-1 (MMP-1)
. ADAMTS-4 and ADAMTS-5
. Cathepsin K
. Hyaluronidase
. Tissue inhibitor of metalloproteinases (TIMP-1)

Correct Answer & Explanation

. ADAMTS-4 and ADAMTS-5


Explanation

The aggrecanases, specifically ADAMTS-4 and ADAMTS-5 (A Disintegrin And Metalloproteinase with Thrombospondin motifs), are the primary enzymes responsible for the early proteolytic cleavage and degradation of aggrecan in osteoarthritis. MMPs (like MMP-13) are more heavily involved in the subsequent degradation of the Type II collagen network.

Question 3675

Topic: Biology, Genetics & Bone Healing

Passage of a sodium ion through a voltage-gated channel leads to which of the following?

. Apoptosis of gram negative bacteria
. Binding of RANKL to osteoblasts
. Inhibition of micturition
. Generation of a nerve action potential
. Deposition of salts in adipose tissue

Correct Answer & Explanation

. Apoptosis of gram negative bacteria


Explanation

Passage of sodium through a voltage-gated channel will lead to generation of a nerve action potential.Voltage-gated channel are shut when the membrane potential is near the resting potential of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold value. When the channels open (in response to depolarization in transmembrane voltage), they allow an inward flow of sodium ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential. This then causes more channels to open, producing a greater electric current across the cell membrane, and so on.Lee et al. present a review article on nerve conduction and needle electromyography studies. They note that the three types of nerve conduction study are motor, sensory,and mixed, of which motor is the least sensitive. In addition, they report that peripheral nerve entrapment initially results in focal demyelination; thus, nerve conduction velocity slows across the site. However, with radiculopathy and nerve root compression, the nerve conduction study may be normal.Catterall presents a review article covering an overview of structural models of voltage-dependent activation, sodium selectivity and conductance, drug block and both fast and slow inactivation. He notes that voltage-gated sodium channels initiate action potentials in nerve, muscle and other excitable cells.Illustration A is a diagram that shows the electrical recordings of an action potential, along with labels of each section of the process.

Question 3676

Topic: 1. General Principles & Basic Science

-Figures 222a and 222b are the radiograph and MRI scan of a 41-year-old man who has had severe leg pain for 6 months despite physical therapy and medications. Examination reveals normal strength and sensation in both lower extremities. What is the most effective treatment option?

. Lumbar interlaminar epidural injection
. Lumbar transforaminal epidural injection
. Posterior lumbar laminectomy
. Posterior lumbar laminectomy and fusion
. Posterior lumbar laminectomy and interbody fusion

Correct Answer & Explanation

. Lumbar interlaminar epidural injection


Explanation

Question 3677

Topic: Biology, Genetics & Bone Healing
Intramembranous ossification during fracture repair is characterized by absence of which of the following elements?
. Alkaline phosphatase
. Osteonectin
. Osteopontin
. Collagen type I expression
. Collagen type II expression

Correct Answer & Explanation

. Collagen type II expression


Explanation

DISCUSSION: Intramembranous ossification occurs through the direct formation of bone without the formation of a cartilaginous intermediate. Clinically, both intramembranous and endochondral ossification occur simultaneously during fracture healing; however, the latter is characterized by the differentiation and maturation of chondrocytes, vascular invasion of a hypertrophic cartilage matrix, and bone formation. Collagens type II and X are cartilage specific and would be characteristic of endochondral ossification, not intramembranous ossification.

Question 3678

Topic: Surgical Anatomy & Approaches

Sciatic nerve

. The sciatic nerve is in the posterior compartment of the thigh and can be palpated at the midpoint between the ischial tuberosity and the greater trochanter when the hip is flexed.
. The obturator nerve is in the medial compartment of the thigh. The femoral nerve is in the anterior compartment of the thigh.
. The peroneal (common peroneal) nerve bifurcates into the deep peroneal and the superficial peroneal nerves which lie in the anterior and lateral compartments of the leg, respectively.

Correct Answer & Explanation

. The sciatic nerve is in the posterior compartment of the thigh and can be palpated at the midpoint between the ischial tuberosity and the greater trochanter when the hip is flexed.


Explanation

(999) Q1-1306:The principal thrombogenic stimulus leading to the production of venous thromboembolic disease during total hip arthroplasty occurs at which time:

Question 3679

Topic: Biology, Genetics & Bone Healing

An osteoprogenitor cell is expected to commit to a bone lineage in the presence of what transcription factor?

. PPARy2
. MyoD
. Sox 9
. C/EBPa
. Runx2

Correct Answer & Explanation

. PPARy2


Explanation

Mesenchymal stem cells are pluripotent cells that can differentiate into many lineages including osteoblasts, adipocytes, myoblasts, chondroblasts, and fibroblasts. Runx2 and Osx appear to be required for differentiation to osteoblastic lines. PPARy2 andC/EBPa are transcription factors leading to adipocytes, MyoD promotes myoblasts, and Sox 9 corresponds to chondroblasts.

Question 3680

Topic: 1. General Principles & Basic Science

A 55-year-old woman with a long history of low back and left lower extremity pain has failed to respond to exhaustive nonsurgical management. MRI scans show bulging and degeneration at L3-4 and L4-5 as well as a normal disk at L2-3 and L5-S1. She undergoes provocative lumbar diskography at L3-4, L4-5, and L5-S1. Post-diskography axial CT images of L3-4 and L4-5 are shown in Figures 6a and 6b, respectively. The injections at L3-4 and L4-5 produce no pain. The injection at L5-S1 produces 10/10 concordant back pain with radiation to the lower extremity. What is the most appropriate recommendation at this time? Review Topic

. Consider fusion surgery
. Intradiskal ozone therapy
. Lumbar laminectomy
. Vertebral augmentation
. Cognitive intervention and exercise

Correct Answer & Explanation

. Consider fusion surgery


Explanation

The results of this patientโ€™s lumbar diskography are equivocal at best. The two disks most likely to be her pain generators, based on their MRI appearance, produced 10/10 pain, however it was nonconcordant and did not reproduce any of her typical left-sided radicular symptoms. The only disk that produced concordant back pain was the normal disk at the L5-S1 level and it reproduced radicular symptoms on the side opposite of her typical pain. Based on these findings, it would be difficult to select a level or levels to include in a lumbar fusion. As such, continued nonsurgical management is the safest treatment option at the current time. Brox and associates reported on a randomized clinical trial comparing lumbar fusion to cognitive intervention and exercise and found similar results in both groups, with significantly less risk in the latter.