Osteoblast
- function
- derived from
- build bone
- come from mesenchymal cells (lineage with cartilage and muscle cells)
Osteoclast
- function
- anatomy
- lineage
- signaling molecule
- break down bone (re-absorption)
- multi-nucleated: fusion of monocytes
- lineage: Hematopoietic stem cells
- signaling molecule: RANKL (critical for differentiation of osteoclasts)
RANKL inhibitor
-used for cancer
Osteocyte
- derived from?
- special feature
- signaling molecule
- osteoblasts trapped in bone matrix they were creating
- as bone begins to mineralize the cells will send out dendritic projections to communicate with other osteocytes
- express RANKL
Bone lining
- quiescent osteoblast
- after wave of bone formation has occurred they will line bone everywhere
- activate immediate formation and recruit other cells
Bone perfusion
- arteries that allow for blood to flow through bone
- peripheral arterial disease leads to osteoporosis
Nutrient artery
-main entrance of blood in bone
What arteries feed diaphysis?
- ascending and descending medullary artery
- connect to nutrient artery
What other arteries are used to profuse bone?
- periosteal arteries
- epiphyseal arteries
How does vit D effect hypertrophy?
- regulate gene expression
- work on hypertrophic cells-allowing them to continue to pass into hypertrophy-sets up matrix that will mineralize
- lack: slows process of mineralization
How does estrogen effect bone growth?
-works on proliferating cells; causes increase in proliferation with spike of estrogen and once those cells finish proliferating the growth plate is closed.
Achodroplasia
- Mutation of?
- What does it prevent?
- How often does it occur?
- Down stream effects
-FGFR3
- Prevention of elongation of long bone
-Epidemiology: every one in 30,000–250,000 total
○ Can cause: sleep apnea due to bend of basocranium (endochondral) which causes stenosis of foramen magnum–spinal chord is pinched; Platyspondyly- excessive lordosis of lumbar–treated with laminectomy
Modeling
- How does it work?
- What causes change
○ Cells work in different areas but at same time; osteoclast in middle, osteoblast on outside
○ Allows for adaptation to increased load or change in shape
Redmodeling
- How does it work?
- What causes change?
○ Cells work in same area but at different time
○ Allows for replacement of bone; driven by loading because of increase of strain on bone which causes microfractures and dead osteocytes must be removed
Rickets
- Cause
- Effect
- Treatment
- Caused by low vit D and calcium
- Will cause widend and irregular growth plate
- Increase calcium and vit D
Intramembranous ossification
- What is it?
- What is responsible?
- Mesenchyme to osteoblast
- Rungsx2 responsible for this type of ossification and mutation in transcription factor of Rungsx2 will cause deficiency in this type of ossification
Endochondral ossifciation
-What is it?
-Mesenchyme to chondroblast to osteoblast
Cleidocranial dysplasia
- Cause
- Symptoms
- Dysfunction of Rungsx2
- Poor formation/missing clavicle/scapula, anterior fontanelle very large, supernumerary teeth (hyperodontia)
Steps in resorption
○ Migration - protosomes
○ Sealing/Ruffle border - Actin ring attaches (creating sealed zone) Ruffle border set up inside sealed zone
○ Acidification- Will demineralize hydroxy epitite,
Enzymatic dissolution - Capescian k- breaks down collagen
Organs involved in bone homeostasis
- Intestines (absorption of Ca)
- Parathyroid (serum Ca)
- Thyroid (calcitonin)
- Kidneys (serum Ca)
3 hormones that control phosphate and calcium in serum?
- PTH
- Vit D- pre-hormone–vit D leads to calcium absorption in body
- Fibroblast growth hormone
Secondary hormones that affect Ca and phosphate in serum?
- Calcitonin: neg regulator of bone absorption
- Insulin
- Thyroid hormone
- Sex hormone
Why is vit D a pre-hormone
-it is activated into active hormone; can make in skin or get from diet
Difference detween Vit D3 and D2
D3 stays in body longer
