Bone remodeling and repair

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Introduction0:00–0:24

Bone remodeling is when old, brittle bone tissue is removed or resorbed and gets replaced by new bone tissue. Remodeling also occurs when reshaping your bones after a fracture or when repairing micro-cracks which form during ordinary activities, especially when your bones are under stress, like after lifting heavy weights.
Now the surface of the bones is covered by this layer called the periosteum, except at the articular cartilages, which are the parts involved in the joints.

Periosteum0:24–0:54

The periosteum consists of an outer fibrous layer which protects the bones and provides attachment for the tendons and the ligaments, and it also has an inner cellular layer which houses progenitor stem cells.
These progenitor stem cells develop into both osteoblasts which secrete the bone matrix, and chondroblasts - which produce cartilage.Now let’s look at the femur - the longest bone in the body.

Bone Structure0:54–2:06

The two ends of the bone that form the joints are called epiphysis, while the shaft of the bone is called the diaphysis.
Looking at the diaphysis, it has an external part; the cortical bone, which consists of many tiny cylinders known as osteons.
Each osteon is made of many lamellae, which are these concentric layers made of an organic part - mostly collagen, and an inorganic part called hydroxyapatite, which is mostly calcium phosphate.
In the center of every osteon is a Haversian canal, which contains the blood supply and innervation for the bone cells. In the center of the bone, is the medullary canal - a hollow space lined by a honeycomb-looking structure called the spongy or cancellous bone.
The medullary canal contains the bone marrow, which is the site of blood cell production. Now, the epiphysis is made of a lot of spongy bone.
And when you look closer at the spongy bone, it’s made of crosslinking tiny roads called trabeculae, which make your bones resistant to mechanical stress, so that they can bear weights without caving in.
And just like the medullary cavity, the spaces in the spongy bone of the epiphysis are occupied by bone marrow. Now, let’s jump into the bone.

Bone Marrow2:06–3:10

That’s where we find two kinds of stem cells – the mesenchymal stem cells, which give rise to osteoprogenitor cells; and the hematopoietic stem cells, the blood-making cells of the bone marrow.
Mesenchymal stem cells are also found in the bone canals, endosteum, and periosteum, and differentiate into osteoblasts.
The hematopoietic stem cells give rise to the lymphoid progenitor cells - which mature and differentiate into lymphocytes like T and B cells, the main cells involved in your adaptive immunity; and the myeloid progenitor cells, which differentiate into red blood cells, platelets, and myeloblasts – the progenitors of basophils, neutrophils, eosinophils and monocytes.
There are a number of growth factors that help these cells develop. For example, osteoblasts release a substance called M-CSF - Macrophage colony-stimulating factor, which helps stimulate myeloid cells like monocytes.

Bone Remodeling3:10–5:09

Now in bone remodeling, the process begins when osteoblasts sense micro cracks at their location, like when your bones are bearing too much weight.
The osteoblasts produce a substance called RANKL - receptor activator of nuclear factor κβ ligand, which binds to RANK receptors on the surface of nearby monocyte precursor cells.
RANKL induces those monocyte precursor cells to fuse together to form a multinucleated osteoclast cell. RANKL also helps the osteoclast mature and activate so that they can start resorbing bones.
The osteoclast starts secreting lysosomal enzymes – mostly collagenase, which digests the collagen protein in the organic matrix.
This drills pits on the bone surface known as the Howship’s lacunae. Osteoclasts also start producing hydrochloric acid - HCl, which dissolves hydroxyapatite into soluble calcium – Ca2+ and phosphate – PO43- ions, and these ions get released into the bloodstream.
There is also a scattering of osteocytes which are trapped within the bony matrix. When these get freed up by the dissolving of bone, they get eaten up or phagocytosed by the osteoclasts.
Man, what a sad way to go! Now to keep the bone resorption under control, the osteoblasts also secrete Osteoprotegerin, which binds to RANKL and prevents it from activating RANK receptors.
This slows down the activation of osteoclasts. Finally, once osteoclasts complete their job, they commit suicide by means of apoptosis.Following bone resorption, osteoblasts start secreting osteoid seam, a substance mainly made of collagen, to fill in the lacunae created by the osteoclasts.
Calcium and phosphate begin to deposit on the seam, forming hydroxyapatite. Also, as osteoblasts keep producing new bony material, many get trapped within tiny lacunae within the bony matrix, and turn into osteocytes.
Bone remodeling is affected by various hormones. The parathyroid glands, the four small pea-like structures located on the thyroid gland in the neck, release parathyroid hormone in response to a drop in blood calcium levels.

Hormonal Regulation5:09–6:20

The parathyroid hormone travels to the bones and stimulates the osteoblasts to release RANKL, which triggers bone resorption.
This allows calcium ions to be released into the bloodstream, and that corrects the deficiency. Now, when the blood calcium level is higher than normal, the parathyroid gland releases less parathyroid hormone to have less bone resorption.
Now, in addition, parafollicular cells in the thyroid gland produce a hormone called calcitonin. High calcitonin levels inhibit bone resorption which results in lower blood calcium levels.
Another factor on bone remodeling is mechanical stress. That’s why bones that bear a lot of weight remodel at such a high rate - a phenomenon called Wolff’s law.
Next, there’s Vitamin D which stimulates intestinal absorption of calcium, which then causes calcitonin levels to increase and that inhibits bone resorption.
Alright, as a quick recap… we have seen that bone remodeling is a continuous process by which bones are resorbed by osteoclasts, and remade by osteoblasts.

Review6:20–6:47

Osteoblasts release RANKL to initiate remodeling, and osteoprotegerin to help turn it off. Bone remodeling is involved in repairing those tiny cracks in your bones due to normal activities, and in helping bones heal after a fracture.