Lecture 7: Bone Formation and Growth Flashcards
Osteoblasts (Obs)
Active bone depositing cells that secrete osteoid
Osteocytes (Ocs)
Mature osteoblasts that have become entrapped within the bone matrix. Maintain gap junction communication and nutrition via dendritic processes in canaliculi
Bone lining cell
Quiescent, inactive osteoblast. Flat and squamous.
Osteoprogenitor (Ops)
MSC-derived progenitor cell for osteoblasts, osteocytes, and bone lining cells. Located in endosteum/cellular periosteum.
Osteoclast (Ocls)
Bone specific macrophage that arises from fusion of monocytes (HSC derived). Large, multinucleated cell that reabsorbs bone by creating Howship’s lacuna and secreting acid and enzymes.
Ruffled border
Active, apical surface of Ocl. Contains folds for more surface area for H+ and enzyme pumps to dissolve bone.
Howship’s lacuna
Resorption bay created by Ocls and sealed off through integrins/f-actin
Basolateral zone
Area in Ocl opposite the ruffled border; contains nuclei and exocytosis activity.
Factors stimulating bone resorption
PTH and RANKL (for RANK receptors) increase Ocl activity, releasing more calcium to the blood
Factors stimulating bone formation
Osteoprotegrin (OPG), calcitonin, and estrogen inhibit Ocl activity, reducing calcium released to the blood.
Osteoporosis
“Porous bone” caused by an imbalance in Ocl/Ob activity.
Osteomalacia
Soft bones and bowed legs due to insufficient Ca + Vit. D; leads to lack of bone mineralization.
Osteopetrosis
Overmineralized bones due to defective Ocls; appears dense but results in fragile structure.
Bone remodeling unit
Cutting cone formed by front of Ocls followed by a closing cone formed by layers of Ops, Obs. Results in resorption of old osteons and creation of new ones.
Types of bone formation
- Intramembranous
- Endochondral
Intramembranous ossification
Ossifications centers from condensed, vascularized mesenchyme. Interstitial bone growth mineralizes and centers merge into trabecular bone. Further appositional growth then on woven bone. Outer/internal mesenchyme become periosteum and endosteum/marrow. Forms flat bones.
Endochondral ossification
Bone replaces a hyaline cartilage precursor structure. Invading blood vessels bring cells + minerals. Starts with periosteal bone collar developing into primary/secondary ossification centers. Growth continues at epiphyseal growth plate with articular cartilage left behind. Forms long bones.
Calcification factors for endochondral ossification
Hypertrophic chondrocytes release alkaline phosphatase and osteocalcin to stimulate calcification.
Bone fracture and repair stages
- Inflammatory phase
- Reparative/regenerative phase
- Remodeling phase
Inflammatory phase
1st stage of bone fracture repair. Torn blood vessels create a hematoma and local Ocs die. Macrophages clear the hematoma, Ocls clear dead Ocs/bone matrix
Reparative/regenerative phase
2nd stage of bone fracture repair. New Ops migrate and differentiate into chondroblasts (low O2 areas) and Obs (high O2 areas). Periosteum is repaired and cartilaginous procallus is deposited, then replaced by spongy bone.
Remodeling phase
3rd phase of fracture repair. Procallus is replaced with woven bone through intramembranous and endochondral ossification. Woven bone is remodeled into compact bone.
Epiphyseal growth plate zones
- Resting
- Proliferation
- Maturation + hypertrophy
- Degeneration + calcification
- Resorption + ossification
Resting zone
Chondrocytes fill a matrix of typical hyaline cartilage
Proliferation zone
Chondrocytes undergo mitotic division, creating “life-saver stacks” of lacunae
Maturation + hypertrophy zone
Chondrocytes expand their lacunae and compress the cartilage
Degeneration + calcification zone
Chondrocytes become apoptotic with pyknotic nuclei; matrix calcifies.
Resorption + ossification zone
Invading vasculature supplies Ops and mineral components; chondrocyte lacunae/matrix is replaced by bone, which rapidly mineralizes
Appositional growth
Addition of bone to inner/outer bone surfaces. Driven by peri/endosteal cells, creating thin lamellae on surfaces.
Haversian remodelling
Remodeling of the inner parts of bones. Forms osteons (Haversian systems). Created by Ocl cutting cone and Ob closing cone.
Sesamoid bones
Bones forming within tendons, e.g. patella
Fibrodysplasia ossificans progressiva
Extra skeletal bones forming from damaged soft tissue. Caused by mutation in Bone Morphogenic Protein receptor.