Passage
Osteoarthritis (OA) is a disorder marked by the deterioration of articular (hyaline) cartilage, the connective tissue lining the ends of bones at most movable joints. The progressive erosion of articular cartilage in OA is thought to be caused by an inflammatory response induced by years of biomechanical stress due to excessive compression and friction. This response involves the release of proteolytic enzymes that break down cartilaginous proteins. The progressive breakdown of articular cartilage ultimately results in complete exposure of the cortical portion of the underlying subchondral bone with narrowing of the joint space. Repeated and abnormal joint stress can also cause the development of osteophytes, or bony growths, that form on the subchondral bone. These degenerative processes cause pain and restrict joint movement.Stem cell therapy, in which injected or grafted stem cells are induced to differentiate into chondrocytes (cartilage cells) , is a potential new treatment for OA. To further understand chondrogenesis, researchers have been studying the molecules that regulate the expression and activity of the transcription factor Sox9, which has been shown to promote chondrocyte differentiation. For example, researchers have found that binding of the growth factor TGF-β to its receptor results in Sox9 activation.MicroRNAs (miRNAs) , which are known to alter gene expression by acting at the translational level, are also potential regulators of Sox9. In particular, miRNA-145 is thought to regulate Sox9 expression by binding to the 3′-UTR of the Sox9 mRNA transcript. After chondrocyte differentiation was induced using TGF-β, researchers used Western blotting to generate an expression profile of Sox9 and β-actin (a protein not regulated by miRNA-145) in mouse stem cells transfected with miRNA-145, anti-miRNA-145, or neither (Figure 1) .
Figure 1 Expression of Sox9 in the presence and absence of miRNA-145 or anti-miRNA-145 following induction of chondrocyte differentiation
Adapted from Yang B, Guo H, Zhang Y, Chen L, Ying D, Dong S. MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9. PLoS ONE. 2011;6(7) :e21679.
-Microscopic examination of tissue samples obtained from the type of bone that becomes exposed in advanced OA is most likely to reveal all of the following EXCEPT:

Question

Passage
Osteoarthritis (OA) is a disorder marked by the deterioration of articular (hyaline) cartilage, the connective tissue lining the ends of bones at most movable joints. The progressive erosion of articular cartilage in OA is thought to be caused by an inflammatory response induced by years of biomechanical stress due to excessive compression and friction. This response involves the release of proteolytic enzymes that break down cartilaginous proteins. The progressive breakdown of articular cartilage ultimately results in complete exposure of the cortical portion of the underlying subchondral bone with narrowing of the joint space. Repeated and abnormal joint stress can also cause the development of osteophytes, or bony growths, that form on the subchondral bone. These degenerative processes cause pain and restrict joint movement.Stem cell therapy, in which injected or grafted stem cells are induced to differentiate into chondrocytes (cartilage cells) , is a potential new treatment for OA. To further understand chondrogenesis, researchers have been studying the molecules that regulate the expression and activity of the transcription factor Sox9, which has been shown to promote chondrocyte differentiation. For example, researchers have found that binding of the growth factor TGF-β to its receptor results in Sox9 activation.MicroRNAs (miRNAs) , which are known to alter gene expression by acting at the translational level, are also potential regulators of Sox9. In particular, miRNA-145 is thought to regulate Sox9 expression by binding to the 3′-UTR of the Sox9 mRNA transcript. After chondrocyte differentiation was induced using TGF-β, researchers used Western blotting to generate an expression profile of Sox9 and β-actin (a protein not regulated by miRNA-145) in mouse stem cells transfected with miRNA-145, anti-miRNA-145, or neither (Figure 1) .

Figure 1 Expression of Sox9 in the presence and absence of miRNA-145 or anti-miRNA-145 following induction of chondrocyte differentiation
Adapted from Yang B, Guo H, Zhang Y, Chen L, Ying D, Dong S. MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9. PLoS ONE. 2011;6(7) :e21679.
-Microscopic examination of tissue samples obtained from the type of bone that becomes exposed in advanced OA is most likely to reveal all of the following EXCEPT:

Quizplus · Accepted Answer

11ecba2d_0fc5_5d55_a3bf_1ff100368ee6_MD0008_00 Based on the passage, the degradation of articular cartilage in advanced OA can ultimately result in complete exposure of the cortical portion of the underlying subchondral bone. A shell of cortical (compact) bone generally surrounds cancellous (spongy) bone. Therefore, the compact bone becomes exposed in advanced OA. Compact (hard) bone is organized into structural units called osteons, or haversian systems, which are made up of lamellae (concentric rings of bone matrix) that surround a central haversian canal, a cylindrical channel that runs parallel to the long axis of bone and through which blood vessels and nerves traverse. Volkmann canals, which run perpendicular to the long axis of bone, allow the passage of blood vessels and nerves between different haversian canals (Choice A). Other cellular components of bone include osteogenic (osteoprogenitor) cells, osteoblasts, osteocytes, and osteoclasts. During bone remodeling, old bone is resorbed (broken down) by osteoclasts and new bone is deposited by osteoblasts. Osteogenic cells are the mitotically active stem cells in bone that initially differentiate into osteoblasts. The osteoblasts then secrete the proteins that form the unmineralized bone matrix called osteoid. Although it is primarily composed of collagen, osteoid eventually becomes mineralized through the precipitation of calcium salts on the surfaces of its collagen fibers. These deposited calcium salts mature into hydroxyapatite crystals, the mineral responsible for bone hardness. Osteoblasts continue to build successive concentric layers of bone, but as the osteoid mineralizes, some osteoblasts become trapped within lacunae (spaces) in the lamellar matrix and are known as (mitotically inactive) osteocytes at this stage. Within each osteon of compact bone, lacunae connect to one another via microscopic channels called canaliculi, which allow osteocyte waste exchange and nutrient delivery (Choices C and D). (Choice B) Chondrocytes make up the cellular component of cartilage, not bone. Educational objective: Compact bone is organized into concentric rings of bone matrix called lamellae. The entire unit of concentrically arranged lamellae surrounding a central haversian canal is known as an osteon, or a haversian system. Within each osteon, lacunae (spaces containing osteocytes) connect to one another via microscopic channels called canaliculi, which allow osteocyte waste exchange and nutrient delivery.