Regulators of Bone Re-modelling


Regulators of Bone Re-modelling

Table of Davidson 25.2 (Page 1062)


Factor | Bone resorption |Bone formation

Parathyroid hormone (PTH) ↑ ↑

Receptor activator of nuclear factor kappa B ligand (RANKL)↑ ↔

Osteoprotegerin (OPG) ↓ ↔

Sclerostin (SOST) ↔ ↓

Interleukin-1 (IL-1) ↑ ↓

Tumour necrosis factor-α (TNF-α) ↑ ↓

Thyroid hormone ↑ ↑

Glucocorticoids ↑ ↓↓

Oestrogen/testosterone ↓ ↑

Mechanical loading ↓ ↑

This are the “Regulators of Bone Re-modelling

Bone Re-modelling Process with the Regualtors

It starts with the attraction of osteoclast precursors in peripheral blood to the target site, probably by local release of chemotactic factors from areas of micro damage. The osteoclast precursors differentiate into mature osteo­clasts in response to RANKL, which is produced by osteocytes, activated T cells and bone marrow stromal cells. RANKL activates the RANK receptor, which is expressed on osteoclasts and precursors. This is blocked by osteoprotegerin (OPG), a decoy receptor for RANKL that inhibits osteoclast formation.

Mature osteoclasts attach to the bone surface by a tight sealing zone, and secrete hydrochloric acid and proteolytic enzymes such as cathepsin K into the space underneath.The acid dissolves the mineral and cathepsin K degrades collagen. When resorption is complete, osteoclasts undergo programmed cell death, and bone formation begins with the attraction of osteoblast precursors to the resorption site. These differentiate into mature osteoblasts, which deposit new bone matrix in the resorption lacuna, until the hole is filled.

Some osteoblasts become trapped in bone matrix and differentiate into osteocytes. These act as biomechanical sensors and produce several molecules that influence bone remodeling and phosphate metabolism. Bone formation is stimulated by Wnt proteins, which bind to and activate lipoprotein related receptor protein 5 (LRP5), expressed on osteoblasts. This process is inhibited by SOST, which is produced by osteocytes.

Ref – Davidson 22 Edition ( Page – 1062)

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