Bone Growth and Resorption – Biochemical and Physiological Control of Bone Remodelling Flashcards
What do osteoblasts arise from
Osteoblasts arise from the same mesenchymal cells that produce fibroblasts and chondrocytes
What controls osteoblast differentiation
Runx2 master transcription factor
IGF-1 & IGF-2
What stimualtes osteoclast differentiation and how does it form from
Bone marrow stromal cells, osteoblasts, and activated T lymphocytes secrete cytokines for osteoclast differentiation
Form by fusion of blood monocytes
What blocks RANK-RANKL pathway
What stimualtes it
osteoprotegerin (OPG)
PGE2
3 specialised regions during osteoclast activation
Ruffled border – in direct contact with bone and contains many microvilli-like structures that increase the surface area for exocytosis of hydrolytic enzymes and secretion of protons
Clear zone – cytoplasm adjacent to the ruffled border that identifies the area of bone to be resorbed
Basolateral region – functions in the exocytosis of digested material
What is intramembranous ossification
Process of bone formation from fibrous membranes
Involved in the formation of the flat bones of the skull, the mandibles, and the clavicles
How does intramembranous ossification occur
Mesenchymal cells migrate and aggregate in specific regions forming ossification centres
Condensation of these cells initiates the process of intramembranous ossification
Transcription factors (Runx2) and growth factors all involved in the differentiation of these cells into osteoblasts
Osteoblasts secrete extracellular matrix and calcium to harden the matrix
How does endochondral ossification occur
Perichondral cells and proliferating chondrocytes secrete PTHrP – promotes chondrocyte division and growth
BMPs promote growth and differentiation of chondrocytes
More mature chondrocytes secrete Ihh (Indian hedgehog) which directs terminal differentiation of neighbouring chondrocytes
Bones grow longer as a result of interstitial growth of cartilage in the epiphysial plate and its continual replacement by bone
What happens to long bones when epiphyseal plate is active
Long bones continue to lengthen as long as the epiphyseal plate is active
Under the influence of growth hormone and insulin-like growth factors
Interstitial growth vs appositional gorwth
Interstitial growth is the lengthening of long bones
Appositional growth is the increase in bone thickness
Wolff’s Law –
bones adapt to stresses/demands placed upon them
What stimulates osteoblasts for remodelling
Following parathyroid hormone (PTH) and vit D3
What proteins does osteoblasts secrete in remodelling
Proteins include collagen fibres, osteocalcin, and osteonectin
What compounds do osteoblasts secrete and what do these compounds do
concentrate calcium and phosphate compounds into vesicles and release the contents into extracellular space
Secreted enzymes free Ca2+ and PO4- from compounds, resulting in high conc of ions that precipitate into hydroxyapatite crystals
Osteoclast function in remodelling
Central region of osteoclast secrete HCl
Also secrete protease enzymes that work at low pH
Combination of acid and enzymes dissolves the calcified hydroxyapatite matrix (including collagen)
Ca2+ released from bone becomes part of ionised Ca2+ pool and can enter the blood
