Devo Lect 14 - Osteogenesis Flashcards
Osteogenesis
Flat bones and long bones; some come from somite (sclerotome) - vertebrae ad ribs; some from lateral plate and migrating mensechymal cells (neural crest)
Intramembraneous ossification
aka dermal bones; face and skull; BMPs; mesenchyme cells migrate, proliferate, condense (adhesion molecules!); form osteoblasts, ECM, calcium salts bind; many layers form; no marrow in these bones, capillaries get really close to living cells
Fontanelle
Some gaps still present in new born skull; filled with collagen; eventually close up and form sutures; very important for birth!
BMPs
bone morphogenetic proteins; growth factors; also important in early embryo%%%
Osteoblasts
Bone precursor cells; secrete collagen-glycoprotein matrix (makes up most of bone) to which calcium salts bind
Endochondral ossification
aka cartilage replacement; most bones; mesenchyme cells migrate, proliferate, condense; form chondrocyte; differentiate into hypertrophic chondrocytes; replaced by osteoblasts; growth plates form; solidify on outside, some spongy bone; bone marrow in the center
Chondrocyte
Cartilage forming cell; secrete ECM;
Osteoclast
break down old bone, recycle ..
Calcification
calcium salts getting incorporated into the ECM, hardens the bone
Growth plate
osteoblasts grow from the middle outward, gradually replace cartilage
Bone marrow function
blood vessels needed to provide nutrition for bone maintenance; bone is living!
Bone fracture healing
Heals basically in the same way bone was formed; hematoma forms: blood clot; fibrocartilaginous callus: chondrocytes form, new ECM that connects the two pieces, new blood vessels; bony callus: cartilage cells die off, replaced by osteoblasts, new bone ECM; some small deviation will be there
PTHrP gene KO mice
resulted in short-limbed dwarfism, shorter bones, domed skull;
PTHrP receptor KO mice
same phenotype as PTHrP KO mice: short-limbed dwarfism
PTHrP
parathyroid hormone related peptide; (PTH increases calcium levels); causes proliferation of chondrocytes, allows the bones to extend
Hedgehog gene in Drosophila
segment polarity gene, keep the orientation; codes for paracrine signaling GF
Hedgehog signaling
Binds to Patched receptor; blocks PKA and Slimb; causes Cubitus interuptus (Ci) to be released so it can turn on genes;
Hedgehog genes in vertebrates
Shh (sonic), Dhh (desert), Ihh (Indian)
Ihh and PTHrP interaction in bone
PTHrP allows cells to proliferate (have receptor), expands that region; chondrocytes committed to hypertorphy make Ihh, which affects perichondrium (via Ptc and Gli) and this causes PTHrP to be released; after a few divisions the cells lose the PTHrP receptor, hypertrophy and apoptosis, osteoblasts become osteocytes and fill in
Timing of ossification
Starts around stage 18, 44 days
