USMLE PRACTICE QUESTION #65
USMLE PRACTICE QUESTION #65
TOPIC: Osteoclast/osteoblast physiology
Today’s question will test your understanding of osteoclast and osteoblast physiology.
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A 42-year-old woman with a history of rheumatoid arthritis presents to her primary care physician for a follow-up visit. She complains of worsening joint pain and stiffness in her hands, knees, and ankles. Her temperature is 36.6°C (97.9°F), blood pressure is 120/80 mmHg, pulse is 85/minute, and respiratory rate is 16/minute. Laboratory studies show an elevated erythrocyte sedimentation rate, C-reactive protein, and an increased level of rheumatoid factor. X-rays reveal joint space narrowing and marginal erosions in the affected joints. Which of the following best describes the mechanism responsible for her worsening symptoms?
A. RANKL binds to RANK receptors, inhibiting NF-κB signaling pathway in osteoclasts
B. RANKL inhibits osteoprotegerin (OPG), leading to increased osteoclast activity
C. RANKL activates Wnt signaling pathway, resulting in osteoclast activation
D. RANKL directly stimulates the production of bone-resorbing enzymes in osteoclasts
E. RANKL increases the expression of RANK receptors on osteoclasts
F. RANKL binds to RANK receptors, activating NF-κB signaling pathway in osteoclasts
G. RANKL activates TGF-β signaling pathway, resulting in osteoclast activation
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The mental model used to answer this question comes from our detailed test-taking skills masterclass. Here’s how to think through this question:
Step 1. Read the last line to determine what the question is asking: Which of the following best describes the mechanism responsible for her worsening symptoms?
Step 2: Is this a first-, second-, or third-order question?
Answer: 3rd order. 1st: Understand the disease’s process, 2nd: Understand what’s behind the worsening symptoms, and 3rd: Identify the actual mechanism behind it.
Step 3: Identify the condition and recognize why it’s getting worse.
Step 4. Ask yourself: “What’s the mechanism?” behind the worsening symptoms.
Step 5. Look at the answer choices and select the option most closely resembling your thoughts from “Step 4” above.
GENERAL ANALYSIS
The question involves the molecular mechanism by which RANK receptor stimulation leads to osteoclast activation, particularly in the context of rheumatoid arthritis and bone resorption.
ANSWER CHOICES:
CHOICE A: RANKL binds to RANK receptors, inhibiting NF-κB signaling pathway in osteoclasts
Explanation: Inhibition of NF-κB would reduce osteoclast activation.
CHOICE B: RANKL inhibits osteoprotegerin (OPG), leading to increased osteoclast activity
Explanation: OPG acts as a decoy receptor for RANKL, preventing it from binding to RANK.
CHOICE C: RANKL activates Wnt signaling pathway, resulting in osteoclast activation
Explanation: Wnt signaling is more associated with osteoblast differentiation and bone formation.
CHOICE D: RANKL directly stimulates the production of bone-resorbing enzymes in osteoclasts
Explanation: While RANKL influences enzyme production, the primary mechanism involves NF-κB signaling.
CHOICE E: RANKL increases the expression of RANK receptors on osteoclasts
Explanation: This would enhance sensitivity to RANKL but is not the primary activation mechanism.
CHOICE F: RANKL binds to RANK receptors, activating NF-κB signaling pathway in osteoclasts
Explanation: The binding of RANKL to RANK activates NF-κB through TRAF6, leading to osteoclast differentiation and activation.
CHOICE G: RANKL activates TGF-β signaling pathway, resulting in osteoclast activation
Explanation: TGF-β is involved in various cellular processes but is not the primary pathway for osteoclast activation via RANKL.
FINAL VERDICT…
The binding of RANKL to its receptor RANK on osteoclast precursors triggers a cascade that activates several signaling pathways, including NF-κB. This activation involves TNF receptor-associated factor 6 (TRAF6) and leads to the differentiation and activation of osteoclasts. The NF-κB pathway is crucial for promoting gene transcription necessary for osteoclastogenesis and bone resorption. This mechanism is essential for understanding how bone remodeling is regulated and how diseases like rheumatoid arthritis can increase bone resorption.
CORRECT ANSWER: F) RANKL binds to RANK receptors, activating NF-κB signaling pathway in osteoclasts
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