Introduction Bone metabolism is a dynamic process that balances bone formation and bone resorption central to this process is the RANK/RANKL/OPG pathway bone formation performed by stimulating osteoblasts and inhibiting osteoclasts bone resorption performed by active osteoclast stimulated by RANKL in normal process stimulated by PTHrP in pathologic process (metastatic disease) Osteoblast Signaling in RANKL pathway Osteoblasts produce RANKL binds RANK and stimulates osteoclastic bone resorption osteoprotegerin (OPG) inhibits osteoclast differentiation, fusion, and activation decoy receptor produced by osteoblasts and stromal cells that binds to and sequesters RANKL alkaline phosphatase Osteoclast Inhibition Osteoclast Inhibition decreases bone resorption Molecules that inhibit bone resorption osteoprotegerin (OPG) calcitonin interacts directly with the osteoclast via cell-surface receptors estrogen (via decrease in RANKL) stimulates bone production (anabolic) and prevents resorption inhibits activation of adenylyl cyclase transforming growth factor beta (TGF beta) (via increase in OPG) interleukin 10 (IL-10) suppresses osteoclasts Osteoclast Activation Osteoclast activation stimulates bone resorption Molecules that stimulate bone resorption RANKL RANKL (ligand) is secreted by osteoblasts and binds to the RANK receptor on osteoclast precursor and mature osteoclast cells PTH activation of its receptor stimulates adenylyl cyclase binds to cell-surface receptors on osteoblasts to stimulate production of RANKL and M-CSF interleukin 1 (IL-1) stimulates osteoclast differentiation and thus bone resorption 1,25 dihydroxy vitamin D stimulates RANKL expression prostaglandin E2 activates adenylyl cyclase and stimulates resorption IL-6 (myeloma) MIP-1A (myeloma) Clinical Implications Osteoporosis can result from loss of function of the OPG gene, leading to constitutive activation of osteoclasts which results in uncontrolled bone resorption and ultimately leads to osteoporosis Osteopetrosis condition caused by a genetic defect resulting in absence of osteoclastic bone resorption a mouse RANKL knockout model creates a osteopetrosis-like condition Paget disease felt to be caused by alterations in cytoplastmic binding to RANK or mutations in the OPG gene Osteolytic bone metastasis found to be mediated by the RANK and RANKL pathway RANKL is produced directly by the cancer cells blocking of RANKL by OPG results in decreased skeletal metastasis in animal models bisphosphonates decrease skeletal events in cancer metastasis Osteolysis following joint arthroplasty polyethylene wear debris is phagocytized by macrophage leads to activation of the macrophage additional macrophages are recruited with release of additional cytokines including RANKL RANKL activates osteoclasts which leads to bone resorption around implants
QUESTIONS 1 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ13.84) Which of the following is true regarding osteoprotegerin (OPG)? QID: 4719 Type & Select Correct Answer 1 It is secreted by osteoclasts 4% (243/5527) 2 It increases bone resorption 4% (197/5527) 3 Binds to prostoglandin E2 before stimulating osteoclasts 4% (248/5527) 4 Osteoprotegerin knock-out mice develop osteopetrosis 6% (352/5527) 5 Binds to and sequesters RANKL 80% (4437/5527) L 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ11.51) Calcitonin plays a role in bone metabolism by which of the following mechanisms? QID: 3474 Type & Select Correct Answer 1 Decreasing osteoclast activity by directly binding to receptor on the osteoclast 59% (2274/3885) 2 Decreasing osteoclast activity by blocking the receptor activator for nuclear factor ligand (RANKL) pathway 19% (743/3885) 3 Increasing osteoblast activity by receptor activator for nuclear factor ligand (RANKL) pathway 5% (206/3885) 4 Decreasing osteoclast activity by stimulating PTH to activate adenylyl cyclase 11% (436/3885) 5 Increasing osteoclast activity by directly binding to receptor on the osteoclast 5% (206/3885) L 3 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ10.51) A 55-year-old female with a history of metastatic breast cancer develops shoulder pain without any trauma. Which of the following is involved with the findings shown in Figures A and B? QID: 3139 FIGURES: A B Type & Select Correct Answer 1 IL-4 3% (73/2772) 2 RANK 77% (2140/2772) 3 TNF-alpha 16% (449/2772) 4 OPG 2% (59/2772) 5 Sox-9 1% (35/2772) L 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ10.227) Which of the following bone modulators primarily utilizes adenylyl cyclase as a mediator for its cellular signaling within osteocytes? QID: 3326 Type & Select Correct Answer 1 SMADs 6% (163/2621) 2 Parathyroid hormone (PTH) 50% (1319/2621) 3 Insulin-like growth factor II (IGF-II) 11% (300/2621) 4 Bone morphogenetic protein 2 (BMP-2) 19% (509/2621) 5 Transforming growth factor-Beta (TGF-ß) 12% (316/2621) L 4 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ09.275) Receptor activator of nuclear-factor kappa-B ligand (RANKL) is an important regulator of bone resorption. Which of the following cells is the MAJOR source of RANKL in bone remodelling? QID: 3088 Type & Select Correct Answer 1 Osteoclasts 14% (419/2951) 2 Osteoblasts 83% (2443/2951) 3 Integrins 1% (30/2951) 4 T cells 1% (27/2951) 5 Macrophages 1% (30/2951) L 5 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ07.210) All of the following substances inhibit osteoclast activity, EXCEPT? QID: 871 Type & Select Correct Answer 1 Tumor necrosis factor-alpha (TNF-a) 67% (1618/2398) 2 Osteoprotegerin 10% (234/2398) 3 Calcitonin 12% (295/2398) 4 Bisphosphonates 3% (71/2398) 5 Denosumab 7% (169/2398) L 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic (OBQ06.149) Which of the following best describes the mechanism by which osteoprotegerin (OPG) plays a role in RANKL-mediated osteoclast bone resorption? QID: 335 Type & Select Correct Answer 1 inhibits RANKL-mediated osteoclast bone resorption by directly binding to RANKL 59% (761/1288) 2 inhibits RANKL-mediated osteoclast bone resorption by directly binding to the RANK receptor on osteoclasts 28% (366/1288) 3 stimulates RANKL-mediated osteoclast bone resorption by directly binding to RANKL 5% (66/1288) 4 stimulates RANKL-mediated osteoclast bone resorption by directly binding to the RANK receptor on osteoclasts 6% (79/1288) 5 stimulates RANKL-mediated osteoclast bone resorption by directly binding to PTH 1% (12/1288) L 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic (OBQ04.146) Which of the following mediators reduces bone resorption? QID: 1251 Type & Select Correct Answer 1 Calcitonin 81% (763/941) 2 RANK ligand 6% (61/941) 3 Interleukin-6 1% (13/941) 4 Parathyroid Hormone 9% (86/941) 5 Dexamethasone 2% (15/941) L 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic
All Videos (2) Podcasts (4) Login to View Community Videos Login to View Community Videos RANK/RANKL/OPG Triad Pathway in Charcot Neuroarthropathy Basic Science - Bone Signaling & RANKL C 9/29/2012 4598 views 4.6 (18) Login to View Community Videos Login to View Community Videos Bone Remodeling and regulation Michael Hughes Basic Science - Bone Signaling & RANKL B 1/26/2012 10711 views 4.8 (91) Basic Science⎪Bone Signaling & RANKL Team Orthobullets 4 Basic Science - Bone Signaling & RANKL Listen Now 8:28 min 10/15/2019 458 plays 5.0 (2) Basic Science⎜Bone Signaling & RANKL Team Orthobullets 4 Basic Science - Bone Signaling & RANKL Listen Now 8:18 min 10/21/2019 118 plays 5.0 (1) Question Session⎪Bone Signaling & RANKL Orthobullets Team Basic Science - Bone Signaling & RANKL Listen Now 13:54 min 11/6/2019 61 plays 5.0 (1) Question Session⎜Bone Signaling, Pediatric Abuse, Metastatic Disease, Prosthetic Joint Infections Orthobullets Team Basic Science - Bone Signaling & RANKL Listen Now 21:1 min 11/11/2019 40 plays 5.0 (1)