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 -Based on the passage, the cells that are most important for the differentiation of OPCs are cells that promote:

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11ecba2d_1004_88c4_a3bf_e57de3738fe0_MD0008_00 Bone is a type of connective tissue that forms the vertebrate endoskeleton. The bone matrix consists of non-living organic materials (eg, collagen) and inorganic materials (eg, calcium phosphate). In addition, several cell types in bone (osteocytes, osteoclasts, osteoblasts) function to maintain the strength and integrity of the skeleton through bone remodeling. During bone remodeling, osteoclasts break down (resorb) old bone and osteoblasts deposit new bone. Specifically, osteoblasts promote the precipitation of calcium and phosphate from the bloodstream and their transfer and incorporation into the bone matrix. The passage states that RANKL is a ligand expressed by osteoblasts that binds RANK, a transmembrane receptor expressed by OPCs. The binding of RANKL on osteoblasts to RANK on OPCs induces downstream signaling pathways that lead to the differentiation of OPCs into mature osteoclasts. Accordingly, osteoblasts, which promote the absorption of calcium from blood to bone tissue, are most important in promoting the activation and differentiation of OPCs. (Choices A, C, and D) According to the passage, osteoclasts secrete proteolytic enzymes and acids that break down the organic and mineral components of bone. As the bone matrix is broken down, mineral components (eg, calcium) are reabsorbed into the bloodstream. Because RANKL is expressed by bone-depositing osteoblasts, osteoclasts that promote the breakdown of bone are not most important in promoting OPC differentiation. Educational objective: Bone remodeling is a continuous process in which osteoclasts (bone-resorbing cells) break down old bone and osteoblasts (bone-depositing cells) secrete new bone matrix. This process functions to maintain the strength and integrity of bone over time. Osteoblasts promote the precipitation of calcium and phosphate from the bloodstream and their transfer and incorporation into the bone matrix. In contrast, osteoclasts secrete acids that break down the mineral components of bone, releasing calcium and phosphate into the bloodstream.

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