WBR0763

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Physiology
Sub Category	SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::Osteogenesis is a complex process that results in the development of bone. Intramembranous and endochondral ossification are 2 processes that result in osteogenesis. Both processes are similar in their conversion of a pre-existing tissue into bone. However, intramembranous and endochondral ossification differ greatly in the means to form bone. Which of the following statements is true regarding osteogenesis?]]
Answer A	AnswerA::Flat bones of the skull are formed by endochondral ossification
Answer A Explanation	AnswerAExp::Flat bones of the skull are formed by intramembranous ossification.
Answer B	AnswerB::Osteoblasts are derived from mesenchymal cells that originate from the neural crest
Answer B Explanation	AnswerBExp::Osteoblasts are derived from mesenchymal cells that originate from the neural crest. In contrast, osteoclasts are derived from macrophage stem cells.
Answer C	AnswerC::Activation of transcription factor CBFA1 is involved in endochondral ossification
Answer C Explanation	AnswerCExp::FA1 CBis a transcription factor involved in the process of intramembranous ossification. In contrast, the two transcription factors Pax1 and Scleraxis are involved in endochondral ossification.
Answer D	AnswerD::Endochondral ossification spreads inwards in long bones from the edges towards the center of the bone
Answer D Explanation	AnswerDExp::Endochondral ossification spreads outward in long bones from the center towards the edges.
Answer E	AnswerE::Osteoblast differentiation is regulated by osteoprotegerin and its ligand
Answer E Explanation	AnswerEExp::Osteoprotegerin, also known as osteoclastogenesis inhibitory factor (OCIF), is a hormone that promotes the conversion of macrophage stem cell into an osteoclast.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Both processes (intramembranous and the endochondral ossification) are required for osteogenesis. Intramembranous ossification does not involve cartilage, and bone is formed directly by the formation of osteoblasts from neural crest-derived mesenchymal cells. These cells secrete collagen-proteoglycan matrix that binds to calcium salts to ultimately calcify the osteoid (pre-bone). As osteoblasts aid in the calcification process, they are trapped within the matrix. Trapped cells are differentiated into osteocytes (mature bone cells). Intramembranous ossification requires the activation of transcription factors, such as CBFA1. On the other hand, endochondral ossification requires cartilage from mesenchyme cells that are ultimately replaced by bone. Endochondral ossification leads to formation of cartilage by chondrocytes that secrete the extracellular matrix. The cartilage forms a model that is eventually replaced by bone, starting at the center and then in the outward direction towards the edges. Osteoblasts form at the edge of the cartilage model and slowly replace cartilage by bone. Involvement of Pax1 and Scleraxis, 2 transcription factors, is required for formation of endochondral ossification. Osteoclasts, derived from macrophage stem cells, are linked to the matrix and pump hydrogen ions onto the matrix to acidify and dissolve it. Osteoprotegerin and its ligand are required for the conversion of macrophage stem cells into osteoclasts. Osteoclasts are under strict hormonal regulation at all times under physiologic conditions. Educational Objective: Osteoblasts are derived from mesenchymal cells that originate from the neural crest, while osteoclasts are derived from macrophage stem cells. References: Gilbert SF. Osteogenesis: The development of bone. in Developmental Biology. 6th ed. Sinauer Associates, Sunderland (MA): 2000. First Aid 2014 page 419]]
Approved	Approved::Yes
Keyword	WBRKeyword::Osteoblast, WBRKeyword::Osteoclast, WBRKeyword::Mesenchyme, WBRKeyword::Neural crest cell, WBRKeyword::Transcription factor, WBRKeyword::Endochondral ossification, WBRKeyword::Intramembranous ossification, WBRKeyword::Osteogenesis, WBRKeyword::Chondrocyte, WBRKeyword::Osteocyte, WBRKeyword::Osteoprotegerin, WBRKeyword::CBF1, WBRKeyword::OCIF, WBRKeyword::Pax1, WBRKeyword::Scleraxis
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