Last update 01 Nov 2024

Siglec-15 x CTSK

Last update 01 Nov 2024

Basic Info

Related Targets

Siglec-15CTSK

Drugs associated with Siglec-15 x CTSK

AB-25E9

Target

CTSK x Siglec-15

Mechanism

CTSK inhibitors [+1]

Active Org.-

Originator Org.

Alethia Biotherapeutics, Inc.

Active Indication-

Inactive Indication

Bone Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Siglec-15 x CTSK

100 Translational Medicine associated with Siglec-15 x CTSK

0 Patents (Medical) associated with Siglec-15 x CTSK

Literatures (Medical) associated with Siglec-15 x CTSK

01 Jun 2023·Journal of Oral Biosciences

Histochemical assessment on osteoclasts in long bones of toll-like receptor 2 (TLR2) deficient mice

Article

Author: Li, Minqi ; Shimizu, Tomohiro ; Ishizu, Hotaka ; Abe, Miki ; Muneyama, Takafumi ; Haraguchi-Kitakamae, Mai ; Hasegawa, Tomoka ; Maruoka, Haruhi ; Hongo, Hiromi ; Yamamoto, Tomomaya ; Yimin ; Amizuka, Norio ; Sasano, Yasuyuki

OBJECTIVEToll-like receptor 2 (TLR2), recognizes a wide variety of pathogen-associated molecular patterns such as lipopolysaccharides, peptidoglycans, and lipopeptides, and is generally believed to be present in monocytes, macrophages, dendritic cells, and vascular endothelial cells. However, no histological examination of osteoclasts, which differentiate from precursors common to macrophages/monocytes, has been performed in a non-infected state of TLR2 deficiency. The objective of this study was to examine the histological properties and function of osteoclasts in the long bones of 8-week-old male TLR2 deficient (TLR2^-/-) mice to gain insight into TLR2 function in biological circumstances without microbial infection.METHODSEight-week-old male wild-type and TLR2^-/- mice were fixed with paraformaldehyde solution, and their tibiae and femora were used for micro-CT analysis, immunohistochemistry, transmission electron microscopy, and real-time PCR analysis.RESULTSTLR2^-/- tibiae and femora exhibited increased bone volume of metaphyseal trabeculae and elevated numbers of TRAP-positive osteoclasts. However, the number of multinucleated TRAP-positive osteoclasts was reduced, whereas mononuclear TRAP-positive cells increased, despite the high expression levels of Dc-Stamp and Oc-Stamp. Although TRAP-positive multinucleated and mononuclear osteoclasts showed the immunoreactivity and elevated expression of RANK and siglec-15, they revealed weak cathepsin K-positivity and less incorporation of the mineralized bone matrix, and often missing ruffled borders. It seemed likely that, despite the increased numbers, TLR2^-/- osteoclasts reduced cell fusion and bone resorption activity.CONCLUSIONIt seems likely that even without bacterial infection, TLR2 might participate in cell fusion and subsequent bone resorption of osteoclasts.

01 Jun 2023·Journal of oral biosciences

Histochemical assessment of osteoclast-like giant cells in Rankl^-/- mice.

Article

Author: Li, Minqi ; Hongo, Hiromi ; Miyamoto, Yukina ; Udagawa, Nobuyuki ; Ishizu, Hotaka ; Hasegawa, Tomoka ; Abe, Miki ; Maruoka, Haruhi ; Yamamoto, Tomomaya ; Haraguchi-Kitakamae, Mai ; Shimizu, Tomohiro ; Amizuka, Norio ; Sasano, Yasuyuki

OBJECTIVESWe examined mice with gene deletion of Receptor activator of nuclear factor-κB (Rank) ligand (Rankl) to histologically clarify whether they contained progenitor cells committed to osteoclastic differentiation up to the stage requiring RANK/RANKL signaling.METHODSThe tibiae and femora of ten-week-old male wild-type, c-fos^-/-, and Rankl^-/- mice were used for immunohistochemistry and transmission electron microscopy (TEM).RESULTSIn Rankl^-/- mice, we observed osteoclast-like giant cells, albeit in low numbers, with single or two nuclei, engulfing the mineralized extracellular matrix. TEM revealed that these giant cells contained large numbers of mitochondria, vesicles/vacuoles, and clear zone-like structures but no ruffled borders. They often engulfed fragmented bony/cartilaginous components of the extracellular matrix that had been degraded. Additionally, osteoclast-like giant cells exhibited immunoreactivity for vacuolar H⁺-ATPase, galectin-3, and siglec-15 but not for tartrate-resistant acid phosphatase, cathepsin K, or MMP-9, all of which are classical hallmarks of osteoclasts. Furthermore, osteoclast-like giant cells were ephrinB2-positive as they were near EphB4-positive osteoblasts that are also positive for alkaline phosphatase and Runx2 in Rankl^-/- mice. Unlike Rankl^-/- mice, c-fos^-/- mice lacking osteoclast progenitors and mature osteoclasts had no ephrinB2-positive osteoclast-like cells or alkaline phosphatase-positive/Runx2-reactive osteoblasts. This suggests that similar to authentic osteoclasts, osteoclast-like giant cells might have the potential to activate osteoblasts in Rankl^-/- mice.CONCLUSIONSIt seems plausible that osteoclast-like giant cells may have acquired some osteoclastic traits and the ability to resorb mineralized matrices even when the absence of RANK/RANKL signaling halted the osteoclastic differentiation cascade.

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