Osteoclasts are multinucleated cells that resorb bone. Although osteoclasts originate from the monocyte/macrophage lineage, osteoclast precursors are not well characterized in vivo. The relationship between proliferation and differentiation of osteoclast precursors is examined in this study using murine macrophage cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB (RANK) ligand (RANKL). Cell cycle–arrested quiescent osteoclast precursors (QuOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments show that QuOPs survive for several weeks and differentiate into osteoclasts in response to M-CSF and RANKL. Administration of 5-fluorouracil to mice induces myelosuppression, but QuOPs survive and differentiate into osteoclasts in response to an active vitamin D3 analogue given to those mice. Mononuclear cells expressing c-Fms and RANK but not Ki67 are detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. These results suggest that QuOPs preexist at the site of osteoclastogenesis and that osteoblasts are important for maintenance of QuOPs.

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The present study investigated the effect on certain physical properties of adding various amounts of hydroxyapatite (HAP) to chitosan sol. Also investigated were connective tissue reactions to a composite membrane that is being developed for possible use in guided tissue regeneration and for the limitation of HA particle migration at sites of implantation. The physical properties evaluated were shrinkage, tensile strength, hardness, calcium ion release, and morphology. Assessment of physical properties indicated that a ratio of HA to chitosan sol of 4/11 by weight is optimal in the preparation of the composite membrane. Subperiosteal implantation of the membranes over rat calvaria revealed that the membranes were well tolerated, with fibrous encapsulation and occasional areas of osteogenesis. Increasing the hydroxyapatite content seems to enhance membrane degradation.

Membranes made of 65, 70, 80, 94, and 100% deacetylated chitin (chitosan) were implanted subperiosteally over the calvaria of 100 rats. Reactions were studied at 1, 2, 4, and 8 weeks after implantation. Membranes prepared with 65, 70, and 80% deacetylated chitin initially elicited marked inflammatory reactions that subsided in time with granulation tissue formation and osteogenesis. Osteocalcin-positive cells were detected immunohistochemically in the granulation tissue. On the other hand, membranes made of 94% deacetylated chitin and chitosan showed mild inflammation and minimal osteogenesis. The results indicate that membranes made of 65, 70, and 80% deacetylated chitin enhance osteogenesis at the site of their implantation. However, the initially severe inflammatory reaction associated with these materials needs to be controlled before the materials would be suitable for clinical application.