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Learning Bone Growth 3: The Osteoclast

Learning Bone Growth 3 – The Osteoclast (OCl), provides a detailed outline of OCl origin from activated monocytes, stimulated by M-CSF, and RANKL. These activated monocytes aggregate to form a multinucleated giant cell, the OCl, which moves to the raw bone surface, seals itself at its margins, creating a specialized acid environment under a ruffled border. The low pH lyses mineral, and a variety of enzymes lyse collagen I. The OCl is highly efficient, and the OB is not. The OCl deletes 3 times its cell volume in its very short 1-2 day lifespan. Refill of this bone by teams of OBs takes 3 months. Perhaps the most important role of the OCl is in bone remodeling. Cortical remodeling begins at age one and effected by the Bone Remodeling Unit or Bone Multicellular Unit, a functional unit which is the effector arm of Wolff’s law wherein bone is formed where needed and deleted where not. The sequence is as follows: deletion -- teams of OCl (8-15) excavate a resorption cavity (RC); OBs lay down a cement line at the periphery of the RC; refill is completed in concentric layers of lamellar bone by teams of OBs. Trabecular remodeling is performed by a similar sequence that occurs constantly in isolated pockets on the endosteal border of individual trabeculae. The steps include: bone lining cells remove surface collagen leaving a raw bone surface (RBS); activation -- marrow derived activated monocytes assemble to become OCls and move to RBS; resorption – OCls mature and remove a finite quantum of mineralized bone; reversal – OCl activity and number declines, replaced by pre-OBs; formation – pre-OBs. become osteoblasts (OBs) which elaborate bone matrix which subsequently mineralizes. A finite unit of bone, termed a quantum is deleted and replaced. CLINICAL CONDITIONS ASSOCIATED WITH DEFECTIVE OSTEOCLAST FUNCTION ARE RARE AND PRESENT AS EXCESSIVE BONE FORMATION AND INCLUDE OSTEOPETROSIS (defects in the RANK/RANKL/OPG signaling axis), and PAGET’S DISEASE, a disorder of disordered remodeling). IF OSTEOCLAST ACTIVITY IS EXCESSIVE, THEN NOT ENOUGH BONE IS FORMED AND OSTEOPOROSIS RESULTS. CONDITIONS ASSOCIATED WITH GENERALIZED INCREASED CLAST ACTIVITY INCLUDE OSTEOPOROSIS ASSOCIATED WITH AGING (imbalance weighted toward increased OCl activation), AND REGIONAL OSTEOPENIA (associated with cancer, inflammation/infection, and trauma) ARISING FROM INCREASED EXPRESSION OF RANKL AND M-CSF INDUCED BY LOCAL CYTOKINES (for example, tumor necrosis factor in rheumatoid arthritis). Consider the OSTEOCLAST as an energy-packed, acid-laden SOS pad, moving on or through bone, scouring the surface, or creating cavities, an exploding star that flames out in one to two days, leaving a divot or a cavity as a sign of its passing.