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Lecture 8

Physiology 4530A/B Lecture 8: Lecture 8

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Western University
Physiology 4530A/B
Frank Beier

Lecture 8: Bone Remodeling and Metabolic Bone Diseases Why remodel bone? - Repair microfractures - Maintenance - Maintain Ca homeostasis Bone Remodeling Cycle Activation  resorption  reversal phase  formation  resting phase (then start over) - Activation: osteoclast precursors recruited to form osteoclasts - Formation: osteoblasts differentiated and fill the bone back in, laying down osteoids that mineralize over time - Whole process takes months - Millions of sites undergoing bone remodeling simultaneously, asynchronously (therefore not regulated by hormones as hormones would be systemic and make everything go on simultaneously; therefore, local signals are driving this) o Signals from osteocyte network, mechanical factors, and inflammation  Mechanical stimulus (e.g. local fracture)  osteoclasts recruited  osteoblasts  bone formation  Prostaglandins are one of the bone cytokines - Basic multicellular unit: this whole area undergoing this process Remodeling in Cortical Bone (Osteonal Remodeling) - Remodeling started on the right side; osteoclasts working on the left side; middle area is osteoblasts forming osteoids; resting phase is quiescent cells covering bone surface - Blood vessels are going thru Haversian canal in the middle (monocytes in blood vessels are source of osteoclast precursors) - Perivascular cells around b.v.s are MSCs which differentiate into osteoblasts Remodeling in Cancellous Bone (Hemiosteonal Remodeling) (just half of cortical remodeling) How do osteoblasts know where to put the bone? - Mechanostat theory: as you are walking, there is bending of bone; when osteoclasts remove part of it they weaken the bone so when you stress the bone there’s more bend than usual; osteocytes sense this and signals to cell surface osteoblasts to make more bone; when mechanical stimulation is at a proper level it stops - BMP theory: when osteoclasts resorb, they dissolve the mineral and organic part, release the material into EC fluid; they release inactive BMPs in bone, activate them which stimulates MSCs to become osteoblast precursors which then differentiate into osteoblasts Diurnal Variation in Bone Remodeling - During the day,
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