Osteoklasti ja kloridi

Kloridiallas kehossa on luun  turn over -prosessissa ajallisesti tärkeä timing-tekijä, siitä ei saa olla puutetta.

https://bmccellbiol.biomedcentral.com/articles/10.1186/s12860-015-0066-4

Background

Bone resorption is important for maintaining mineral homeostasis, adapting to functional loading, and healing damaged and fractured sites. The process of bone consumption is regulated by the number of osteoclasts, and relies heavily on the ability of individual osteoclasts to secrete H⁺ through the ruffled border, thus lowering the extracellular pH (pH_o) at a delimited bone surface.

The first demonstration of an acidic area adjacent to osteoclasts utilized the fluorescent probe acridine orange [1]. Later, it was shown—using pH microelectrodes—that osteoclasts can acidify the contact zone with a culture dish to less than pH 3 within a few minutes [2]. It has been proposed that extracellular acidification is a key step for the dissolution of the apatite-containing mineralized matrix [3, 4] and osteoclast intracellular pH (pH_i) regulation [5, 6, 7, 8]; in addition, H⁺ secretion creates a suitable pH, in the resorption lacuna, for enzymes to degrade the organic matrix [9]. Therefore, bone resorption depends on the expression and activity of H⁺-secreting proteins at the osteoclast ruffled border.

Several mechanisms have been implicated in contributing to the acidification of the resorption lacuna; such as: H⁺ secretion through vacuolar H⁺-ATPase (V-ATPase) [10] and a H⁺-coupled Cl⁻ secretion, by chloride channel 7 (ClC-7) [11]. Furthermore, the Na⁺/H⁺ exchanger, NHE-10 isoform [12], and a H⁺ conductance have been reported to regulate pH_i by means of acid secretion [5, 6, 13].

The movement of acid–base equivalents across the plasma membrane is crucial for pH_i regulation [14, 15]. At the osteoclast plasma membrane, the base-transporters include NBCn1 (Na⁺-HCO₃ ⁻ cotransporter) [16], and AE2 (Cl⁻/HCO₃ ⁻ anion exchanger) [12, 17, 18]; and the acid-transporters include V-ATPase, Na⁺/H⁺ exchanger and the aforementioned H⁺ conductance [5, 6, 13]. In addition to its role in osteoclast pH regulation, H⁺ secretion by the V-ATPase works in parallel with ClC-7 [19], which have been proposed as the key components of cellular machinery for extracellular acidification at the ruffled border (Fig. 1). It should also be noted that pH_i regulation is related to the translocation of several ions (as Na⁺ and Cl⁻) across the plasma membrane by specific proteins.