Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces:​ an in vitro and ex vivo study of remodeling bone

Dodds, Robert A.; Connor, Janice R.; James, Ian E.; Rykaczewski, Elizabeth Lee; Appelbaum, Edward; Dul, Edward; Gowen, Maxine

Affiliations

¹SmithKline Beecham Pharmaceuticals, Department of Cellular Biochemistry, King of Prussia, Pennsylvania, U.S.A

²SmithKline Beecham Pharmaceuticals, Department of Gene Expression Sciences, King of Prussia, Pennsylvania, U.S.A

Abstract

Osteopontin is a phosphorylated glycoprotein believed to be secreted by osteoblasts and deposited into the bone matrix to facilitate osteoclast adhesion or to initiate osteoid mineralization. Previously we have presented contradictory evidence that osteoclasts express osteopontin mRNA in human remodeling bone. The aim of this study was to ascertain whether osteoclasts synthesize and deposit osteopontin in resorption lacunae. We characterized expression of osteopontin mRNA and protein expression in both intramembranous and endochondral ossification, as well as remodeling bone, in the human osteophyte. Osteopontin mRNA was expressed in osteoclasts with tartrate-resistant acid phosphatase (TRAP) positivity within resorption lacunae. The osteoclasts and immediate resorption surfaces also expressed osteopontin. However, osteopontin mRNA and protein were weak (transient) or undetectable in osteoblasts at adjacent bone formation sites; no osteopontin expression was observed in the osteoid, although occasional reactivity was observed in osteocytes and the mineral-osteoid interface. In contrast, osteopontin was highly expressed in the osteoblasts and matrix of woven bone during intramembranous and endochondral ossification. The matrix expression correlated with mineralization; however, in some instances osteopontin deposition was observed prior to mineralization. Similarly, osteopontin expression was evident in cartilage matrix, solely at foci of mineralization. Chondroclasts expressed osteopontin mRNA and protein; the surfaces of resorbed calcified cartilage also expressed osteopontin. Abnormal, unmineralized matrices apparently lacked deposited osteopontin, but were nevertheless resorbed by osteoclasts; the osteoclasts and resorbed surfaces expressed no osteopontin protein. That osteoclasts are responsible for the deposition of osteopontin was confirmed in vitro, whereby resorption pits in whale dentine and bovine bone slices, produced by isolated human osteoclasts, contained deposited osteopontin. Osteopontin may facilitate the adhesion (or detachment) of the osteoclast to the bone surface. Alternatively, the possibility that osteopontin may act as a postresorptive signal to recruit osteoblasts, or to polarize and direct the mineralization of the formed osteoid, is discussed.

Links

DOI: 10.1002/jbmr.5650101109

PubMed: 8592943

WoS: A1995TD33700008

History

Received: 1995-01-30

Revised: 1995-05-30

Accepted: 1995-06-6

Cited Works (5)

Year	Entry
1990	Reinholt FP, Hultenby K, Oldberg A, Heinegård D. Osteopontin: a possible anchor of osteoclasts to bone. Proc Natl Acad Sci USA. June 1990;87(12):4473-4475.
1993	Ingram RT, Clarke BL, Fisher LW, Fitzpatrick LA. Distribution of noncollagenous proteins in the matrix of adult human bone: evidence of anatomic and functional heterogeneity. J Bone Miner Res. September 1993;8(9):1019-1029.
1994	Zhou H, Chernecky R, Davies JE. Deposition of cement at reversal lines in rat femoral bone. J Bone Miner Res. March 1994;9(3):367-374.
1989	Butler WT. The nature and significance of osteopontin. Connect Tissue Res. 1989;23(2-3):123-136.
1993	Denhardt DT, Guo X. Osteopontin: a protein with diverse functions. FASEB J. December 1993;7(15):1475-1482.

Cited By (11)

Year	Entry
2000	Semba I, Ishigami T, Sugihara K, Kitano M. Higher osteoclastic demineralization and highly mineralized cement lines with osteocalcin deposition in a mandibular cortical bone of autosomal dominant osteopetrosis type II: ultrastructural and undecalcified histological investigations. Bone. September 2000;27(3):389-395.
2022	Lamarche BA, Thomsen JS, Andreasen CM, Lievers WB, Andersen TL. 2D size of trabecular bone structure units (BSU) correlate more strongly with 3D architectural parameters than age in human vertebrae. Bone. July 2022;160:116399.
2002	Everts V, Delaissé JM, Korper W, Jansen DC, Tigchelaar-Gutter W, Saftig P, Beertsen W. The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res. January 2002;17(1):77-90.
1999	Nanci A. Content and distribution of noncollagenous matrix proteins in bone and cementum: relationship to speed of formation and collagen packing density. J Struct Biol. June 30, 1999;126(3):256-269.
2003	Young MF. Bone matrix proteins: their function, regulation, and relationship to osteoporosis. Osteoporos Int. March 2003;14(suppl 3):S35-S42.
2005	Takai E. Modulation of Bone Cell Mechanotransduction [PhD thesis]. Columbia University; 2005.
2002	Egerer AK. The Relationship Between the Osteonal Cement Line and Bone Strength [PhD thesis]. Loma Linda University; June 2002.
2010	Janeiro C. The Effect of Bone Quality on Osteoclastic Bone Resorption [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; May 2010.
2013	Nikel O. Role of Osteopontin and Osteocalcin in the Organic-Inorganic Interface of Bone Tissue [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; November 2013.
2013	Adler B. High Fat Diet Rapidly Suppresses B Lymphopoiesis by Disrupting the Supportive Capacity of the Bone Marrow Niche [PhD thesis]. Stony Brook, NY: Stony Brook University; August 2013.
2007	Wu Y-L. Interaction of Bone Cells With Biomimetic Hydroxyapatite Gelatin Nanocomposites Towards Developing Bone Tissue Engineering [PhD thesis]. University of Minnesota; December 2007.