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                   3.33  Transverse section of a Haversian system undergoing remodelling. Osteoclasts resorb bone tissue; osteo-
                   blasts differentiate from progenitor cells and initiate formation of new systems (schematic).

                   proteins. The capacity of osteoclasts to undergo polari-  to accumulation of unmineralised bone matrix, resulting
                   sation, coordinate specific movements and bind to the  in the disease known as rickets. Bone resorption is fur-
                   extracellular matrix is largely attributable to this complex  ther regulated by local paracrine and autocrine factors
                   network of protein filaments (F-actin) and actin-binding  (cytokines, various interleukins, growth factors and pros-
                   proteins (e.g. vinculin). The circular alignment of F-actin in  taglandins, thyroid hormone). Per unit of time, osteoclasts
                   the clear zone is a morphological expression of increased  resorb approximately three times as much bone matrix as
                   cellular activity in an active osteoclast. It is regulated hor-  that laid down by osteoblasts.
                   monally, by calcitonin and parathyroid hormone.   Structurally, osteoclasts are similar to chondroclasts and
                      Active osteoclasts contain abundant mitochondria.  it has been proposed that these terms refer to the same
                   Lying internal to the ruffled border, these organelles  cell type.
                   exhibit a high rate of aerobic metabolism. Due to the pres-
                   ence of large numbers of vacuoles and dense bodies, the  Bone matrix
                   cytoplasm of osteoclasts appears loosely structured. The  Bone matrix is composed of:
                   vacuoles are associated with the endocytic, autophagocytic
                   and exocytic functions of the cell.              ·  an organic component (collagen fibres and ground
                      The cell membrane of osteoclasts incorporates several   substance rich in glucosamine) and
                   classes and subclasses of receptors that aid in maintaining   ·  an inorganic component (minerals).
                   the seal between the cell and the bone matrix (integrin,
                   vitronectin receptors), as well as myeloid antigens.  ORGANIC COMPONENT (COLLAGEN FIBRES AND
                      Bone resorption occurs in two ways: formation of   GROUND SUBSTANCE)
                   lacunae (Howship’s lacunae, resorption bays) by osteo-  Type I collagen fibres are the main component (approxi-
                   clasts lying on the bone surface, or resorption of bone  mately 90%) of the organic substance of bone. During
                   along vessels by one or more osteoclasts.      bone mineralisation, these fibres provide a framework
                      The bone resorption process consists of two phases.  (crystallisation scaffold) for the deposition of hydroxyapa-
                   In the extracellular phase, the bone is degraded by acids  tite crystals (Ca [PO ] [OH] ). Glycosaminoglycans and
                                                                               10  4 6   2
                   and lytic enzymes released into the space between the  proteoglycans (chondroitin-4-sulfate, chondroitin-6-sul-
                   osteoclast and the bone. In the intracellular phase, these  fate, keratin sulfate) make up 1–2% of the bone matrix.
                   degradation products are taken up at the ruffled border  Together with lipids (5–10%), the structural proteins of
                   by endocytosis and further broken down in cytoplasmic  the collagen fibres comprise around one third of the dry
                   vesicles (primarily lysosomes).                weight of bone tissue.
                      Osteoclasts are highly mobile cells. The texture of the
                   bone matrix is an important determinant of the degree of   INORGANIC COMPONENT (MINERALS)
                   their mobility. After resorbing bone in a particular area,  The inorganic component of bone matrix, which accounts
                   osteoclasts detach themselves from the bone surface and  for approximately two-thirds of the dry weight of bone, is
                   migrate to another area before reattaching and resuming  composed predominantly of calcium phosphate (85–90%),
                   the bone degradation process.                  calcium carbonate (8–10%), magnesium phosphate (1.5%) and
                      The activity of osteoclasts is inhibited by calcitonin,  calcium fluoride (0.3%). These minerals form a crystal lattice
                   and stimulated by 1,25-dihydroxycholecalciferol (vitamin  (consisting mostly of hydroxyapatite) alongside the collagen
                   D ) and parathyroid hormone. Vitamin D  deficiency leads  fibres, surrounded by proteoglycan rich ground substance.
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