skeletal

Welcome to Dr. Kate Brilakis' Learning Portal

Glucocorticoids...

= stress

Hormonal control of bone remodeling:
Calcitonin and Parathyroid Hormone (PTH)

The synthesis and degradation of bone is controlled by the
RANKL system.

PTH stimulates the secretion of RANKL

pathology

Hyperparathyroidism

overactivation of osteoclasts due to parathyroid tumors stimulating the over secretion of PTH leading to
very high blood Ca+ levels

OPG is stimulated by estrogen.
OPG blocks RANKL from binding to RANK so decreases osteoclast activity.
low estrogen levels leads to increased osteoclast activity and weaker bones.

Bone marrow
is the tissue found in the medullary cavities and spongy bone of long bones.
There's red bone marrow (myeloid tissue) and yellow bone marrow (fatty tissue).
Red marrow houses stem cells which are able to differentiate into WBCs used to fight infections, RBCs which carry O2 and platelets which participate in clot formation.
Yellow marrow is stored fatty tissue but also contains stem cells which give rise to fat, cartilage, and bone.

Bone marrow transplants are used to treat conditions where the bone marrow isn't functioning properly, such as leukemia, aplastic anemia, and sickle cell anemia. They can also be used to restore bone marrow function after high-dose chemotherapy or radiation therapy.

the enzyme aromatase converts testosterone into estradiol.

aromatase is found in fat tissue, the brain, bone, and other areas, with fat cells being a major site of activity.

GH imbalance

Parathyroid hormone (PTH) acts to resorb calcium from the bone and increase calcium resorption by the kidneys increasing
blood Ca+ levels.

Rickets is a condition that causes a child’s bones to soften and weaken. This makes them bend and warp, often leading to bowed legs. It also causes bone pain and makes them break more easily. The most common cause of rickets is a vitamin D deficiency. This occurs when a child doesn’t get enough vitamin D from the foods they eat or exposure to the UV radiation from the the sun.

RANKL is released by osteoblasts. RANKL binds to RANK receptors on the surface of stem cells and triggers them to differentiate into osteoclasts.

This is a another example of a ligand/receptor system.

AND

Finding a match for a bone marrow transplant involves identifying a donor with compatible Human Leukocyte Antigens (HLAs), which are proteins found on the surface of white blood cells. The ideal match has the same HLA markers as the recipient.

In men,
estrogen (estradiol) and testosterone both influence the OPG/RANKL balance though its effects are less pronounced than in women.

Osteoclasts
release enzymes that release calcium from bone, decalcifying the matrix.

bone remodeling

osteoporosis

OPG acts as a decoyreceptor that inhibits RANKL's signaling. The balance between RANKL and OPG affects bone mass.

Osteoblasts secrete a new matrix of collagen and calcium salts.

The human body has 206 bones
There are 26 bones in the foot
The hand and wrist contains 54 bones
The femur is the longest and strongest bone
The stapes, in the middle ear, is the smallest and lightest bone
Only the hyoid bone isn't connected to another bone
Only 10% of the world's animals have an internal skeletal system

Rickets

Excessive production of GH in children (before the epiphyseal plates fuse) results in gigantism and continued growth of long bones.

RANKL
stands for 'Receptor Activator of NF-κB Ligand'.
It is a cytokine (cell messenger) crucial for bone resorption. It acts as a ligand, binding to its receptor RANK on stem cells.

This triggers them to differentiate into osteoclasts leading to bone resorption.

the bone remodeling process

Calcitonin and PTH are antagonists

When the area around the osteoblast calcifies into this matrix, the osteoblast becomes trapped in this bony matrix within a space called the lacuna and transforms into an osteocyte.

Calcitonin acts to reduce blood Ca+ levels.
Calcitonin inhibits the activity of osteoclasts and decreases the resorption of calcium by the kidneys.