Passage Bone remodeling is the continuous, microscopic process by which bone tissue throughout the body is resorbed and re-deposited. Proper regulation of bone remodeling is necessary to maintain bone strength and prevent the onset of conditions of fragile bone such as osteoporosis. Patients with such conditions have increased fracture risk and generally exhibit decreased activity of osteoblasts (bone-depositing cells), leading to reduced bone density and weakening of the bone matrix. However, some cases can occur due to overactive osteoclasts (multinucleated cells that mediate bone resorption). Osteoclasts resorb bone by secreting proteolytic enzymes and acids into the adjacent extracellular space. These enzymes degrade the organic matrix of bone, and the acid causes the dissolution and release of the mineral components of bone, such as calcium, potassium, and magnesium. Generally, less than 1% of adult bone is occupied by active osteoclasts.Osteoclast differentiation and activation is thought to be related to the RANK/RANKL signaling pathway. RANKL, expressed as a membrane-bound or secreted protein, serves as the ligand for RANK, a transmembrane receptor. In bone tissue, RANK is expressed by precursors of mature osteoclasts, also known as osteoclast progenitor cells (OPCs). RANKL is expressed by osteoblasts adjacent to OPCs, and the binding of RANKL to RANK in these neighboring cells causes downstream effects through recruitment of TRAF6, an intracellular protein. TRAF6 activates multiple downstream signaling cascades, but only four of these directly mediate the development of mature osteoclasts from OPCs. In one of the four pathways, the transcription factor NF-kB is activated, which leads to increased expression of the proto-oncogene c-Fos. Subsequently, c-Fos interacts with another transcription factor known as NFATc to promote the expression of genes related to osteoclast-specific development and function in OPCs (Figure 1). Figure 1 RANK/RANKL signaling induces differentiation of OPCs into osteoclasts -The information in the passage suggests that increased activity of RANK is most likely due to signaling involving which of the following hormones?

Question

Quizplus · Accepted Answer

11ecba2d_1007_20d9_a3bf_7943052992ef_MD0008_00 Endocrine glands secrete hormones that travel through the bloodstream and bind target receptors in specific tissues, evoking responses that promote the maintenance of physiological homeostasis. For example, parathyroid hormone (PTH) and calcitonin are hormones that maintain calcium homeostasis by regulating calcium absorption and bone remodeling. Specifically, low blood calcium levels stimulate the parathyroid glands to secrete PTH, which then promotes several processes to elevate blood calcium levels. One of these processes involves a PTH-induced increase in osteoclast activity. PTH promotes increased resorption of bone by osteoclasts, which leads to the release of calcium from bone and its uptake into the bloodstream, ultimately increasing serum calcium levels. According to the passage, the activation of the RANK receptor by RANKL stimulates the differentiation of OPCs into mature osteoclasts, which can actively break down (resorb) bone. Because PTH leads to increased activity of osteoclasts, this hormone is likely associated with increased activity of RANK and subsequent stimulation of osteoclast maturation and activity. (Choice B) Calcitonin is secreted by the thyroid gland in response to high blood calcium levels and opposes PTH activity by decreasing the activity of osteoclasts. Therefore, calcitonin would be associated with decreased (not increased) RANK activity and reduced activation of osteoclasts. (Choice C) The anterior pituitary secretes growth hormone (GH) to induce tissue growth, including bone development. GH can stimulate osteoblast activity to increased bone matrix deposition. Because GH is a key promoter of bone growth in children and increases the rate of cell turnover in adults, it is most likely associated with decreased RANK activity (ie, less breakdown of bone by osteoclasts). (Choice D) Glucagon, a hormone secreted by the pancreas, is a key regulator of blood glucose levels (not bone remodeling). In the setting of low blood glucose, glucagon stimulates the breakdown of glycogen in the liver to increase blood glucose levels. Educational objective: To regulate calcium homeostasis, parathyroid hormone (PTH) and calcitonin act antagonistically to each other. PTH is secreted in response to low blood calcium levels and stimulates bone resorption by osteoclasts, causing an increase in blood calcium. In contrast, calcitonin is secreted in response to high blood calcium levels and decreases osteoclast activity, ultimately decreasing blood calcium.

Passage Bone Remodeling Is the Continuous, Microscopic Process by Which Bone