bone cell biology Flashcards
bone function
function: its a connective tissue
Serves as infrastructure, bone marrow (5% of Body weight), reservoir of Ca and phosphate
Specialized CT: bone is calcified ECM
Bone as CT: Cells (osteoblasts, osteocytes, osteoclasts (activated by PTH to leach calcium, inhibited by calcitonin (from thyroid), theres also a matrix
Bone matrix
inorganic component (70%): Calcium and phosphorous=hydroxy apatite, 99% of the bodys Ca is stored in bone hydroxyapatite
Organic component (30%)= osteoid
type 1 collagen confers eosinophilia on stain
proteoglycans: less than in cartilage
Glycoproteins: promote hydroxyapatite formation (osteocalcin is a bone specific glycoprotein, promotes mineralization)
Why is bone so hard: hydroxyapatite
Bone vs hyaline cartilage
Bone: Mineral-70% Water-25% Collagen- type 1 Neuronal and vascular structures- present
Hyaline cartilage: Mineral: none Water: 75% Collagen: type 2 Neuronal/vascular structure: none
osteoblasts
osteoblasts are specialized fibroblasts
Growth factors, such as bone morphogenetic proteins (BMPs) induce mesenchymal stem cells MSCs to differentiate into osteoblasts
groups of osteoblasts are required to make OSTEOID: type 1 collagen and glycoproteins (single osteoblasts cant do this) most osteoblasts are in the periosteum
Bone formation is completed by osteocalcin-mediated deposition of CA++ in the osteoid (no hydroxyapatite no wt bearing)
Osteoblasts have Runx2 and osteocalcin
Osteocytes
occupy lacunae between lamellae of bone matrix
1 osteocyte per lacuna
Osteocytes=90% of bone cells
Dendrites penetrate the matrix and bind other osteocytes via gap junctions
Function: mechanosensation to regulate bone remodeling, secretion of sclerostin to inhibit bone growth
Osteocytes live a long time (25 year half life)
Osteoclasts
destroy bone matrix for remodeling
Multinuclear, via development from macrophage like cells that fuse together
Reside in hollowed out areas of matrix termed HOWSHIPS lacunae
Have ruffled borders that attach ECM forming microenvironment for bone resorption
Osteoclasts are regulated by hormones (PTH activates osteoclasts–CO2–> H2CO3–>HCO3–>H+ –> acidifies microenvironment
Lysosomes–> cathepsin K –>microenvironment
Calcitonin (thyroid hormone) inhibits osteoclasts
Diseased osteoclasts= pagets disease
Where are bone cells located
Bone is lined by outer/periosteum and inner/endosteum layers of connective tissue
Osteoblasts are located in the periosteum with smaller number the endosteum
Osteocytes reside within lacunae of the bony matrix lying between the periosteum and endosteum
Osteoclasts are mostly found attached to bony matrix on the endosteal side
Compact vs spngy bone
Compact aka cortical: 80% of long bones, dense/no cavitation
Spongy: aka cancellous and trabecular: 20% cavitated
Flat bones (calvaria): 2 plates of compact bone surrounding dipöle of spongy bone
long bones: diaphysis(shaft)-compact with spongy bone lining the marrow
Epiphyses (end)- caps of compact bone surrounding spongy bone
Long bones are 80% cortical and trabecular
Osteon: cylinder with concentric lamellae=unit of bone structure
Lamellae have lacunae that harbor osteocytes, connected via canaliculi
The innermost lamella surrounds the haversion canal (contains blood vessels, nerves, lymph)
Bone development and regeneration
Primary bone is woven
Secondary bone is lamellar and mature
Bone develops in 2 ways:
- intramembranous: osteoblasts deposit osteoid directly onto reticular connective tissue (NOT a membrane)
- Endochondral: osteoblasts deposit osteoid onto cartilage
Endochondral: bone forms on hyaline cartilage (at the diaphysis: osteoblasts invade calcified cartilage secrete osteoid–> ossification
At epiphysis: same
Articular carilage remains at the ends of bone
Epiphyseal plate cartilage remains v diaphysis and epiphysis for growth in length (zones of epiphyseal growth)
How long bones become long
sex steroid hormones –> pituitary–>growth hormone (GH somatotropin) –> liver –>IGF1 –> epiphyseal plate
Zone of cartilage proliferation is activated by IGF1
Zone of hypertrophy: 20% of fractures happen here
Zone of calcification: collagen 2 is replaced by collagen 10
Zone of ossification: osteoblasts deposit collagen 1 causing eosinophilia
Fracture Repair in 4 simple steps
- Macrophages remove debris
- fibroblasts and chondroblasts secrete a callus of fibrocartilage
- Osteoblasts replace fibrocarilaginous callus with bony callus
- primary bone is replasced by lamellar secondary bone
Bone tissue engineering: difficult fractures require: grafting
Remodeling never stops: new skeleton every 10 years
Osteoclasts excavate bone which is then replaced by activated osteoblasts
Diseases of remodeling:
Osteopetrosis: dense heavy bone; mutant osteoclasts lack a ruffled border
Osteoporosis: resorption by osteoclasts outpaces osteogenesis=hollow fragile bones
Osteoporosis
28 million americans 2/3rds women
post menopausal women lose 2% bone mass annually treatable
Breaks at wrist, hip spine
Prevention: dietary Ca++, vitamin D (improves absorption of CA++), weight bearing excersizes help
Screening: bone minderal density scanner (compare BMD with young normal subjects (t score: number of deviations below the young normal mean)
Therapeutic targets: osteoclasts, osteoblasts
How are osteoclasts made
PTH induces stromal cells in the bone marrow to secrete 3 factors: RANKL, OPG and M CSF
These factors act on monocytes/macrophages
MCSF: induces proliferation of monocytes/macrophages
RANKL: induces their differentiation into osteoclasts
OPG: osteoprotegerin: antagonizes RANKL by binding to its receptor: hence OPG inhibits osteoclast production
Theoretically, osteoporosis can be managed by regulating the activity of opposing bone cells
Osteoblasts: inhibited by leptin (obesity –> risk for osteoporosis)
induced by BMP, induced by PTH
Osteoclasts: inhibited by calcitonin, OPG
Induced by RANKL, induced by PTH
