title: Thyroid status affects number and localization of thyroid hormone receptor expressing mast cells in bone marrow.
abstract: Thyroid hormone (T(3)) plays a key role in endochondral ossification. The process relies on the coordinated synthesis and degradation of cartilage matrix and is disrupted in juvenile hypothyroidism, leading to abnormal skeletal development. Mast cells synthesize and store matrix-degrading enzymes. We examined whether thyroid status influences skeletal mast cell distribution in growing rats to determine whether they might modulate the actions of T(3) in bone. Tibiae were collected for histological, histochemical, immunohistochemical, and immunofluorescence analysis. Mast cells were increased throughout the bone marrow in hypothyroid rats compared with euthyroid, thyrotoxic, and hypothyroid-thyroxine replaced animals. Large numbers were present in metaphyseal marrow adjacent to the growth plate in hypothyroid animals and cells were distributed evenly throughout the marrow. Very few mast cells were present in metaphyseal marrow in other groups, but their numbers increased with increasing distance from the growth plate. T(3) receptor alpha1 (TRalpha1) was expressed in the nucleus and cytoplasm of skeletal mast cells, whereas TRalpha2 and TRbeta1 were restricted to the cytoplasm. Localization of TRs was not affected by altered thyroid status. Thus, disrupted endochondral ossification in hypothyroidism may be mediated in part by skeletal mast cells, which express TR proteins and may function as T(3) target cells.
authors.affiliation: Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.
authors.forename: T
authors.initials: T
authors.lastname: Siebler
authors.forename: H
authors.initials: H
authors.lastname: Robson
authors.forename: M
authors.initials: M
authors.lastname: Bromley
authors.forename: D A
authors.initials: DA
authors.lastname: Stevens
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
authors.forename: G R
authors.initials: GR
authors.lastname: Williams
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002452:Cell Count; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013971:Thyrotoxicosis / Q000378:metabolism / Q000473:pathology; D013974:Thyroxine / Q000627:therapeutic use
chemical_list: D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013974:Thyroxine